Crystallization and structure of a plant peptide deformylase

ABSTRACT

This invention relates to the crystal structure of a plant peptide deformylase polypeptide and methods of using the structure to design compounds that modulate the activity of the polypeptide.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 11/542,989, filed Oct. 3, 2006, which claims priority to U.S. Provisional Application Ser. No. 60/835,823 filed Aug. 4, 2006, the entire contents of which are herein expressly incorporated herein by reference.

STATEMENTS REGARDING FEDERALLY SPONSORED RESEARCH

The invention was funded in part by Grant No. MCB-MCB-0240165 awarded by the National Science Foundation (NSF). The government may have certain rights in the invention.

TECHNICAL FIELD

This invention relates to the crystallization and structure of plant peptide deformylase and methods of using the structure.

BACKGROUND

Peptide deformylase (DEF; EC 3.5.1.88) is a metallopeptidase that catalyzes the removal of an N-formyl group from N-formyl methionine, which is the initiating amino acid residue for prokaryotically translated proteins. DEF is an essential enzyme and mutations, deletions, or insertions in the DEF gene, or inhibition of enzymatic activity, are lethal to prokaryotic organisms. For decades DEF was believed to be exclusively restricted to prokaryotes because protein translation in eukaryotic organisms initiates with an unformylated methionine residue. The restriction to prokaryotic organisms and the essentiality of DEF have made this enzyme the molecular target of many research efforts directed towards the development of broad-spectrum antibiotics, which would have little or no mammalian toxicity. In 2000 the existence of DEF in the chloroplasts of higher plants was reported, and it was also discovered that actinonin, a potent inhibitor of DEF, was phytotoxic to all plant species. The lethality of actinonin to a wide range of plants, including many agriculturally significant weed species, suggests that DEF is an essential and highly conserved enzyme in plants, and inhibitors targeting this enzyme could potentially serve as a new class of broad-spectrum herbicides as well as selectable markers.

Accordingly, plant peptide deformylase (DEF) polypeptides provide an attractive target for crystallization and structural studies which can lead to the identification and synthesis of new broad-spectrum herbicides and selectable markers with high specificity towards plant DEF.

SUMMARY

Provided herein are crystalline forms of a peptide deformylase, and atomic coordinates derived therefrom, useful for designing and identifying compounds that modulate the activity of the peptide deformylase. Accordingly, in one embodiment, a crystalline form of a polypeptide comprising the amino acid residues of SEQ ID NO:1, is provided. In some aspects, the crystalline form includes a structure characterized by tetragonal space group symmetry P4₁2₁2 and unit cell of dimensions a, b, and c. In some aspects, a is about 40 Å to about 60 Å, b is about 40 Å to about 60 Å, and c is about 120 Å to about 160 Å. In other aspects, α=β=γ=90°. In some aspects, the polypeptide is a peptide deformylase isolated from Arabidopsis thaliana.

In some embodiments, the crystalline form includes a coordinated metal ion selected from the group of consisting of Fe, Zn, and Ni, and any combination thereof. In one aspect, the metal ion is coordinated by amino acid residues Cys171, His 213, and His217 of SEQ ID NO:1.

In another embodiment, a crystalline form of a polypeptide including a structure defined by one or more structure coordinates of Arabidopsis thaliana peptide deformylase amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His 217, and Tyr178 according to Table 1, is provided. In general, structures derived from these crystalline forms encompass structures having coordinates that differ by a root mean square deviation of less than about 1.5 Å, 0.75 Å, or 0.35 Å, or any deviation in this range, when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1. In some aspects, amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 include the active site of the peptide deformylase. In some aspects, the polypeptide includes an amino acid sequence having at least 75%, at least 85%, or at least 95%, or any percent in this range, amino acid sequence identity to SEQ ID NO:1.

In other embodiments, a crystalline form of a polypeptide provided herein also includes a ligand complexed with the polypeptide. In some aspects, the ligand is a small molecule.

In another embodiment, a crystalline form of a polypeptide that includes the amino acid residues of SEQ ID NO:1 and an atomic structure characterized by the coordinates of Table 1, is provided.

In yet another embodiment, a machine-readable medium embedded with information that corresponds to a three-dimensional structural representation of a crystalline form of a polypeptide as provided herein.

In one embodiment, a computer system including a database containing information on the three dimensional structure of a crystalline form of an Arabidopsis thaliana peptide deformylase polypeptide and a user interface to view the information, is provided. In some aspects, the computer system includes information related to diffraction data obtained from a crystalline form comprising SEQ ID NO:1. In other aspects, the computer system of includes information related to an electron density map of a crystal comprising SEQ ID NO:1.

In another aspect, a computer system provided herein includes information related to the structure coordinates of Table 1 or homologous structure coordinates for the amino acid residues of SEQ ID NO:1 that have a root mean square deviation of non-hydrogen atoms of less than about 1.5 Å, 0.75 Å, 0.35 Å, or any percent in this range, when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1.

In other aspects, a computer system provided herein includes information related to the structure coordinates for one or more amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His 217, and Tyr178 according to Table 1, or similar structure coordinates for the amino acids including a root mean square deviation of non-hydrogen atoms of less than about 1.5 Å, 0.75 Å, 0.35 Å, or any percent in this range, when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1.

In another embodiment, a method of identifying a candidate compound that binds to the active site of Arabidopsis thaliana peptide deformylase polypeptide, is provided. The method includes comparing the atomic structure of the compound with a three-dimensional structure of a crystalline form of an Arabidopsis thaliana peptide deformylase polypeptide and computationally identifying a candidate compound for an ability to bind to the Arabidopsis thaliana peptide deformylase. In some aspects, the candidate compound binds to the active site of the Arabidopsis thaliana peptide deformylase. In other aspects, comparing the atomic structure of the compound with a three-dimensional structure of a crystalline form of an Arabidopsis thaliana peptide deformylase polypeptide includes employing a computational means to perform a fitting operation between the compound and at least one binding site of the peptide deformylase.

In some embodiments, the candidate compound identified by a computational method provided herein can be synthesized and screened for the ability to bind a plant peptide deformylase in vitro or in vivo. In some aspects, the compound is an herbicide.

In another embodiment, a method of identifying a candidate compound that binds to the active site of Arabidopsis thaliana peptide deformylase polypeptide, is provided. The method includes comparing the atomic structure of the compound with a three-dimensional structural representation of a crystalline form provided herein and computationally identifying a candidate compound for an ability to bind to the active site of Arabidopsis thaliana peptide deformylase.

In yet another embodiment, a method of computationally designing a candidate compound that binds to Arabidopsis thaliana peptide deformylase polypeptide, is provided. The method includes comparing the atomic structure of chemical entities, or fragments thereof, with a three-dimensional structural representation of a crystalline form of a polypeptide provided herein; identifying chemical entities capable of associating with the three-dimensional structural representation of a crystalline form of a polypeptide; and assembling the chemical entities, or fragments thereof, into a single molecule to provide the structure of the candidate compound. In some aspects, the candidate compound binds to the active site of Arabidopsis thaliana peptide deformylase.

In another embodiment, a method of identifying a region of Arabidopsis thaliana peptide deformylase polypeptide that contacts a compound, is provided. The method includes obtaining X-ray diffraction data for a crystal of Arabidopsis thaliana peptide deformylase; obtaining X-ray diffraction data for a complex of a Arabidopsis thaliana peptide deformylase and the compound; subtracting the X-ray diffraction data from the peptide deformylase with the X-ray diffraction data obtained from the complex to obtain the difference in the X-ray diffraction data; obtaining phases that correspond to X-ray diffraction data obtained for the peptide deformylase; correlating the data to generate a difference Fourier image of the compound; and locating the region of Arabidopsis thaliana peptide deformylase contacted by the compound. In some aspects, the compound is actinonin.

In another embodiment, a method of modifying an inhibitor of Arabidopsis thaliana peptide deformylase activity, is provided. The method includes obtaining a crystal including an Arabidopsis thaliana peptide deformylase polypeptide and an inhibitor; obtaining the atomic coordinates of the crystal; correlating the atomic coordinate data with one or more molecular modeling techniques; identifying at least one modification predicted to effect the interaction of the inhibitor with the polypeptide; and modifying the inhibitor based on the prediction. In one aspect, the modification is a computer generated modification. In other aspects, the modification is a physical modification made to the structure of the inhibitor. In one aspect, the crystal comprises the amino acid residues of SEQ ID NO:1.

In other aspects, the one or more molecular modeling techniques are selected from the group consisting of graphic molecular modeling and computational chemistry. In another aspect, obtaining the atomic coordinates of the crystal includes detecting the interaction of the inhibitor to one or more amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 of SEQ ID NO:1.

The details of one or more embodiments of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1A depicts a polyacrylamide gel showing that limited trypsinolysis creates a core protein that retained activity and remained soluble in the absence of high salt concentrations.

FIG. 1B depicts the amino acid sequence of the AtDEF peptide (SEQ ID NO: 1).

FIG. 2A depicts a ribbon representation of crystallized AtDEF2. The cylinders represent helices and the arrows represent sheets.

FIG. 2B depicts a slab view of the ribbon representation of trypsinolyzed AtDEF2 highlighting the active-site-metal binding ligands (1 Cys and 2 His) from motifs II and III, respectively (EGCLS (SEQ ID NO: 15) and QHEXXH (SEQ ID NO: 16)).

FIG. 3 depicts a graph of substrate specificity comparison of AtDEF1 and AtDEF2.

FIG. 4 depicts a comparison of amino acid sequence conservation of the three motifs in AtDEF1 and 2 and bacterial DEFs (SEQ ID NOS: 2-5).

FIG. 5 depicts a molecular model of the N-terminal residues from the D1 polypeptide docked into the active site of Arabidopsis thaliana peptide deformylase.

FIG. 6 depicts a phylogenetic analyses comparing Motif 1 (SEQ ID NO: 6), Motif 2 (SEQ ID NO:7) and Motif 3 (SEQ ID NO: 8) of plant AtDEF1 peptide deformylase with the amino acid sequence of other peptide deformylase sequences.

FIG. 7 depicts a phylogenetic analyses comparing Motif 1 (SEQ ID NO: 9), Motif 2 (SEQ ID NO: 10) and Motif 3 (SEQ ID NO: 11) of plant AtDEF2 peptide deformylase with the amino acid sequence of other peptide deformylase sequences.

FIG. 8 depicts a phylogenetic analyses comparing Motif 1 (SEQ ID NO: 12), Motif 2 (SEQ ID NO: 13) and Motif 3 (SEQ ID NO: 14) of various peptide deformylase amino acid sequences.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

Provided herein are novel crystalline forms of peptide deformylase polypeptides and atomic coordinate information related to such crystals. Also provided are methods of using such information to identify, design and/or modify compounds that modulate the activity of a peptide deformylase. In addition, computer systems that include such information are provided. The crystal structures and information derived therefrom are suitable for designing and identifying, for example, broad spectrum herbicides. Such herbicides can be used, for example, to inhibit or prevent the growth of undesirable vegetation.

The crystal structure is based, at least in part, on the discovery of a plant nuclear gene that encodes a chloroplast targeted peptide deformylase polypeptide. The gene has substantial homology to bacterial peptide deformylase. The deduced translation of this nucleic acid sequence reveals the presence of three conserved protein motifs associated with prokaryotic peptide deformylase (see e.g., FIGS. 6, 7, and 8). Nucleic acid and amino acid sequences for plant peptide deformylases are disclosed in U.S. Pat. No. 6,730,634, issued May 4, 2004, and U.S. Patent Application Publication No. 20040088755, the contents of which are incorporated herein by reference.

It is to be understood that the crystalline form of a plant peptide deformylase from which the atomic structure coordinates of the invention can be obtained is not limited to wild-type Arabidopsis thaliana peptide deformylase polypeptide, or a truncated form of the polypeptide (see e.g., SEQ ID NO:1) as provided herein. Indeed, the crystals may comprise mutants of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1. Mutants can be obtained by replacing at least one amino acid residue in the sequence of the wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 with a different amino acid residue, or by adding or deleting one or more amino acid residues within the wild-type sequence and/or at the N- and/or C-terminus of the wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1. Preferably, such mutants will crystallize under crystallization conditions that are substantially similar to those used to crystallize the wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1.

The types of mutants contemplated by this invention include conservative mutants, non-conservative mutants, deletion mutants, truncated mutants, extended mutants, methionine mutants, selenomethionine mutants, cysteine mutants and selenocysteine mutants. A mutant may have, but need not have, Arabidopsis thaliana peptide deformylase activity. Preferably, a mutant displays biological activity that is substantially similar to that of the wild-type polypeptide or that of SEQ ID NO:1.

It will be recognized by one of skill in the art that the types of mutants contemplated herein are not mutually exclusive; that is, for example, a polypeptide having a conservative mutation in one amino acid may in addition have a truncation of residues at the N-terminus.

In addition, conservative or non-conservative amino acid substitutions can be made to amino acids of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 that are implicated in the active site of the polypeptide (e.g., amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 of SEQ ID NO:1). Such conservative or non-conservative substitutions can affect, e.g., the affinity with which wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 binds to a substrate. In certain embodiments, the conservative or non-conservative amino acid substitutions can increase the affinity with which wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 binds to a substrate.

Conservative amino acid substitutions are well-known in the art, and include substitutions made on the basis of a similarity in polarity, charge, solubility, hydrophobicity and/or the hydrophilicity of the amino acid residues involved. Typical conservative substitutions are those in which the amino acid is substituted with a different amino acid that is a member of the same class or category, as those classes are defined herein. Thus, typical conservative substitutions include aromatic to aromatic, apolar to apolar, aliphatic to aliphatic, acidic to acidic, basic to basic, polar to polar, etc. Other conservative amino acid substitutions are well known in the art. It will be recognized by those of skill in the art that generally, a total of about 20% or fewer, typically about 10% or fewer, most usually about 5% or fewer, of the amino acids in the wild-type polypeptide sequence can be conservatively substituted with other amino acids without deleteriously affecting the biological activity and/or three-dimensional structure of the molecule, provided that such substitutions do not involve residues that are critical for activity. The following abbreviations are used for amino acids throughout this disclosure: A=Ala=Alanine, T=Thr=Threonine, V=Val=Valine, C=Cys=Cysteine, L=Leu=Leucine, Y=Tyr=Tyrosine, I=Ile=Isoleucine, N=Asn=Asparagine, P=Pro=Proline, Q=Gln=Glutamine, F=Phe=Phenylalanine, D=Asp=Aspartic Acid, W=Trp=Tryptophan, E=Glu=Glutamic Acid, M=Met=Methionine, K=Lys=Lysine, G=Gly=Glycine, R=Arg=Arginine, S=Ser=Serine, H=His=Histidine.

In some embodiments, it may be desirable to make mutations in the active site of a polypeptide, e.g., to reduce or completely eliminate deformylase activity. Mutations that will reduce or completely eliminate the activity of a particular protein will be apparent to those of skill in the art. For example, the amino acids identified in Table 1 could be mutated in order to reduce or eliminate the binding activity of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1.

The amino acid residue Cys (C) is unusual in that it can form disulfide bridges with other Cys (C) residues or other sulfhydryl-containing amino acids (“cysteine-like amino acids”). The ability of Cys (C) residues and other cysteine-like amino acids to exist in a polypeptide in either the reduced free —SH or oxidized disulfide-bridged form affects whether Cys (C) residues contribute net hydrophobic or hydrophilic character to a polypeptide.

While in most instances the amino acids of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 will be substituted with genetically-encoded amino acids, in certain circumstances mutants may include genetically non-encoded amino acids. Alternatively, in instances where the mutant will be prepared in whole or in part by chemical synthesis, virtually any non-encoded amino acids may be used, ranging from D-isomers of the genetically encoded amino acids to non-encoded naturally-occurring natural and synthetic amino acids.

Conservative amino acid substitutions for many of the commonly known non-genetically encoded amino acids are well known in the art. Conservative substitutions for other non-encoded amino acids can be determined based on their physical properties as compared to the properties of the genetically encoded amino acids.

In some instances, it may be particularly advantageous or convenient to substitute, delete from and/or add amino acid residues to wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 in order to provide convenient cloning sites in cDNA encoding the polypeptide, to aid in purification of the polypeptide, etc. Such substitutions, deletions and/or additions that do not substantially alter the three dimensional structure of the native Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 will be apparent to those having skills in the art. These substitutions, deletions and/or additions include, but are not limited to, His tags, BirA tags, intein-containing self-cleaving tags, maltose binding protein fusions, glutathione S-transferase protein fusions, antibody fusions, green fluorescent protein fusions, signal peptide fusions, biotin accepting peptide fusions, and the like.

Mutations may also be introduced into a polypeptide sequence where there are residues, e.g., cysteine residues, that interfere with crystallization. Such cysteine residues can be substituted with an appropriate amino acid that does not readily form covalent bonds with other amino acid residues under crystallization conditions; e.g., by substituting the cysteine with Ala, Ser or Gly. Any cysteine located in a non-helical or non-beta-stranded segment, based on secondary structure assignments, are good candidates for replacement.

It should be noted that the mutants contemplated herein need not exhibit deformylase activity. Indeed, amino acid substitutions, additions or deletions that interfere with the binding activity of wild-type Arabidopsis thaliana peptide deformylase or the sequence of amino acids set forth in SEQ ID NO:1 are specifically contemplated by the invention. Such crystalline polypeptides, or the atomic structure coordinates obtained therefrom, can be used to provide phase information to aid the determination of the three-dimensional X-ray structures of other related or non-related crystalline polypeptides.

Also contemplated are homologs of the Arabidopsis thaliana peptide deformylase. The present invention provides a computer-assisted method for homology modeling an Arabidopsis thaliana peptide deformylase homolog including: aligning the amino acid sequence of an Arabidopsis thaliana peptide deformylase homolog with the amino acid sequence of Arabidopsis thaliana peptide deformylase SEQ ID NO:1 and incorporating the sequence of the Arabidopsis thaliana peptide deformylase homolog into a model of Arabidopsis thaliana peptide deformylase derived from structure coordinates set forth in Table 1 to yield a preliminary model of the Arabidopsis thaliana peptide deformylase homolog; subjecting the preliminary model to energy minimization to yield an energy minimized model; remodeling regions of the energy minimized model where stereochemistry restraints are violated to yield a final model of the Arabidopsis thaliana peptide deformylase homolog.

As used herein, the term “homolog” refers to the polypeptide molecule or the nucleic acid molecule which encodes the polypeptide, or a functional domain from said polypeptide from a first source having at least about 30%, 40% or 50% sequence identity, or at least about 60%, 70% or 75% sequence identity, or at least about 80% sequence identity, or more preferably at least about 85% sequence identity, or even more preferably at least about 90% sequence identity, and most preferably at least about 95%, 97% or 99% amino acid or nucleotide sequence identity, with the polypeptide, encoding nucleic acid molecule or any functional domain thereof, from a second source. The second source may be a version of the molecule from the first source that has been genetically altered by any available means to change the primary amino acid or nucleotide sequence or may be from the same or a different species than that of the first source. Homology modeling is further discussed below.

Accordingly, provided herein are crystalline forms of a plant peptide deformylase. Referring to FIG. 1A, limited trypsinolysis creates a core protein that retained activity and remained soluble in the absence of high salt concentrations. Analysis of wild-type and proteolyzed AtDEF2 on an 8-16% gradient SDS-PAGE. Trypsinolysis produces a truncated DEF2 with a mobility shift corresponding to a 3 kDa loss in molecular mass from AtDEF2, a 24.598 kDa enzyme. The truncated DEF2, which loses its hexahistidyl sequence, was subsequently separated from undigested DEF2 by loading the digested sample onto a HiTrap® affinity column (Amersham Pharmacia) and collecting the flowthrough. Undigested DEF2 remained bound to the column. Referring to FIG. 1B, the amino acid sequence of the truncated DEF2 polypeptide is provided.

It is understood that the term “crystalline form” includes a polypeptide associated with a plant peptide deformylase can include just the polypeptide, or the polypeptide complexed with a metal, a ligand, or any other chemical entity suitable for crystallization with the polypeptide. An exemplary polypeptide includes Arabidopsis thaliana peptide deformylase, or fragments thereof, suitable for crystallization. Such fragments include optionally, the crystal may include a coordinated metal ion selected from the group of consisting of Fe, Zn, Ni, or combinations thereof. Thus, “crystalline form” and “crystal” refer to a composition comprising a polypeptide complex in crystalline form. The term “crystal” includes native crystals, heavy-atom derivative crystals and poly-crystals. “Native Crystal” refers to a crystal wherein the polypeptide complex is substantially pure.

Referring to FIG. 2A, the crystal structure of DEF2 was determined by molecular replacement and refined to a resolution of 2.7 Å. “Molecular Replacement” refers to the method of calculating initial phases for a new crystal of a polypeptide whose structure coordinates are unknown by orienting and positioning a polypeptide whose structure coordinates are known within the unit cell of the new crystal so as to best account for the observed diffraction pattern of the new crystal. Phases are then calculated from the oriented and positioned polypeptide and combined with observed amplitudes to provide an approximate Fourier synthesis of the structure of the polypeptides comprising the new crystal (Jones et al., 1991, Acta Crystallogr. 47:753-70; Brunger et al., 1998, Acta Crystallogr. D. Biol. Crystallogr. 54:905-21).

The overall fold of the enzyme resembles the α+β conformation of known bacterial peptide deformylases, with an r.m.s deviation of about 1.04 Å on main chain atoms relative to the E. coli enzyme. The largest differences occur in the orientation of the C-terminal helix (helix 3) and the conformation of the loop between β strands 2 and 3, which form part of the five-stranded central sheet. Motif I, II and III are colored blue, green and pink, respectively. The active site metal, modeled as zinc due to the conditions of crystallization, is a space-filled sphere in the middle of the structure. Referring to FIG. 2B, a slab view of the ribbon representation of trypsinolyzed AtDEF2 highlighting the active-site-metal binding ligands (1 Cys and 2 His) from motifs II and III, respectively (EGCLS (SEQ ID NO: 2) and QHEXXH (SEQ ID NO: 3)) is provided. As used herein, the term “active site” refers to regions on a protein or a structural motif of a protein that are directly involved in the function or activity of the peptide deformylase.

As used herein, the terms “binding site” or “binding pocket” refer to a region of a polypeptide or a molecular complex comprising the polypeptide that, as a result of the primary amino acid sequence of the polypeptide and/or its three-dimensional shape, favorably associates with another chemical entity or compound including ligands or inhibitors.

The crystalline form can include the tetragonal space group symmetry P4₁2₁2 and includes a unit cell having dimensions a, b, and c; wherein a is about 40 Å to about 60 Å, b is about 40 Å to about 60 Å, and c is about 120 Å to about 160 Å; and wherein alpha=beta=gamma=90 degree. In some aspects, a is about 49 Å to about 52 Å, b is about 49 Å to about 52 Å, and c is about 143 Å to about 147 Å.

“Unit Cell” refers to the smallest and simplest volume element (i.e., parallel piped-shaped block) of a crystal that is completely representative of the unit or pattern of the crystal, such that the entire crystal can be generated by translation of the unit cell. The dimensions of the unit cell are defined by six numbers: dimensions a, b and c and angles α, β and γ (Blundel et al., 1976, Protein Crystallography, Academic Press). A crystal is an efficiently packed array of many unit cells. “Tetragonal Unit Cell” refers to a unit cell in which a≠b≠c; and α=β=γ90°. “Crystal lattice” refers to the array of points defined by the vertices of packed unit cells. “Space group” refers to the set of symmetry operations of a unit cell. In a space group designation (e.g., C₂) the capital letter indicates the lattice type and the other symbols represent symmetry operations that can be carried out on the unit cell without changing its appearance. “Asymmetric Unit” refers to the largest aggregate of molecules in the unit cell that possesses no symmetry elements that are part of the space group symmetry, but that can be juxtaposed on other identical entities by symmetry operations.

When a crystal is placed in an X-ray beam, the incident X-rays interact with the electron cloud of the molecules that make up the crystal, resulting in X-ray scatter. The combination of X-ray scatter with the lattice of the crystal gives rise to nonuniformity of the scatter; areas of high intensity are called diffracted X-rays. The angle at which diffracted beams emerge from the crystal can be computed by treating diffraction as if it were reflection from sets of equivalent, parallel planes of atoms in a crystal (Bragg's Law). The most obvious sets of planes in a crystal lattice are those that are parallel to the faces of the unit cell. These and other sets of planes can be drawn through the lattice points. Each set of planes is identified by three indices, hkl. The h index gives the number of parts into which the a edge of the unit cell is cut, the k index gives the number of parts into which the b edge of the unit cell is cut, and the l index gives the number of parts into which the c edge of the unit cell is cut by the set of hkl planes. Thus, for example, the 235 planes cut the a edge of each unit cell into halves, the b edge of each unit cell into thirds, and the c edge of each unit cell into fifths. Planes that are parallel to the bc face of the unit cell are the 100 planes; planes that are parallel to the ac face of the unit cell are the 010 planes; and planes that are parallel to the ab face of the unit cell are the 001 planes.

When a detector is placed in the path of the diffracted X-rays, in effect cutting into the sphere of diffraction, a series of spots, or reflections, are recorded to produce a “still” diffraction pattern. Each reflection is the result of X-rays reflecting off one set of parallel planes, and is characterized by an intensity, which is related to the distribution of molecules in the unit cell, and hkl indices, which correspond to the parallel planes from which the beam producing that spot was reflected. If the crystal is rotated about an axis perpendicular to the X-ray beam, a large number of reflections is recorded on the detector, resulting in a diffraction pattern.

The unit cell dimensions and space group of a crystal can be determined from its diffraction pattern. First, the spacing of reflections is inversely proportional to the lengths of the edges of the unit cell. Therefore, if a diffraction pattern is recorded when the X-ray beam is perpendicular to a face of the unit cell, two of the unit cell dimensions may be deduced from the spacing of the reflections in the x and y directions of the detector, the crystal-to-detector distance, and the wavelength of the X-rays. Those of skill in the art will appreciate that, in order to obtain all three unit cell dimensions, the crystal can be rotated such that the X-ray beam is perpendicular to another face of the unit cell. Second, the angles of a unit cell can be determined by the angles between lines of spots on the diffraction pattern. Third, the absence of certain reflections and the repetitive nature of the diffraction pattern, which may be evident by visual inspection, indicate the internal symmetry, or space group, of the crystal. Therefore, a crystal may be characterized by its unit cell and space group, as well as by its diffraction pattern.

Once the dimensions of the unit cell are determined, the likely number of polypeptides in the asymmetric unit can be deduced from the size of the polypeptide, the density of the average protein, and the typical solvent content of a protein crystal, which is usually in the range of 30-70% of the unit cell volume (Matthews, 1968, J. Mol. Biol. 33:491-497).

The diffraction pattern of a crystal is related to the three-dimensional shape of the molecules that constitute the crystal by a Fourier transform. It has been established that diffraction patterns of a crystal can result from X-ray diffraction as well as Laue, electron or neutron diffraction. X-ray diffraction has been the most widely used methods for determining macromolecular structures. It is therefore used by way of illustration to discuss the processes of diffraction data collection and subsequent structure determination. The scope of the present invention is, however, by no means limited only to X-ray diffraction analyses of crystalline forms of polypeptides. After enough diffraction data are collected for a crystal, the process of determining the solution is in essence a re-focusing of the diffracted X-rays to produce a three-dimensional image of the molecule in the crystal. Since lenses capable of focusing X-ray radiation do not yet exist, the structure determination can be done via mathematical operations that simulate the re-focusing process.

“X-ray Diffraction” refers to a type of wave interference created when high energy X-ray radiation interacts with any obstruction in its traveling path. The obstruction is often in the form of a crystal of protein, nucleic acid, or inorganic compound. The electrons that surround the atoms in the crystal, rather than the atomic nuclei, are the entities which physically interact with the incoming X-ray photons. When X-ray radiation hits the atoms in a crystal, they make the electronic clouds of the atoms move as does any electromagnetic wave. The re-emitted X-ray radiation gives rise to constructive or destructive interferences. This phenomenon is called X-ray diffraction. In X-ray crystallography, the X-ray diffraction patterns of closely spaced lattices of atoms in the crystal are recorded and then analyzed to reveal the structural nature of the crystal. For example, the spacing between the crystal lattices can be determined using Bragg's law. X-ray diffraction is widely used in chemistry and biochemistry to determine the structures of an immense variety of molecules, including inorganic compounds, DNA and proteins. X-ray diffraction is commonly carried out using single crystals of a material, but if these are not available, microcrystalline powdered samples may also be used, although this requires different equipment. A detailed discussion on X-ray diffraction may be found in Chapter 4 in “Principles of Protein X-ray Crystallography” by Drenth, second edition 1999, Springer-Verlag Inc.

“Bragg's Law” refers to the principle that defines the diffraction conditions that give rise to constructive interferences. When the phase shift of the incident radiation is proportional to 2π, the condition can be expressed as: πλ=2d sin(θ), where n is an integer; λ is the wavelength of the X-ray radiation, or radiations caused by moving electrons, protons and neutrons; d is the spacing between the planes in the atomic lattice, and θ is the angle between the incident ray and the scattering planes.

“Crystallization” in the context of protein X-ray crystallography refers to the processes during which soluble proteins are transformed into their crystalline forms. Crystals of a protein can be grown out of its solution state under experimental conditions that allow controlled phase transition. Such experimental conditions include a mixture of multiple solutions that often contain an aqueous solution of the target protein, a solution of one or a mixture of precipitants, and one or more compounds that contribute to the overall pH or ionic strength of the final mixture.

Provided herein are crystalline forms of a plant peptide deformylase polyepeptide, or a deformylase complexed with other molecules or chemical entities. Analysis of such crystalline forms of a polypeptide provides data in the form of structure coordinates. Exemplary structure coordinates for Arabidopsis thaliana peptide deformylase polypeptide are provided in Table 1. As used herein, the term “atomic coordinates” or “structure coordinates” refers to mathematical coordinates that describe the positions of atoms in crystals of a plant peptide deformylase in Protein Data Bank (PDB) format, including X, Y, Z and B, for each atom. The diffraction data obtained from the crystals are used to calculate an electron density map of the repeating unit of the crystal. The electron density maps may be used to establish the positions (i.e., coordinates X, Y and Z) of the individual atoms within the crystal. Those of skill in the art understand that a set of structure coordinates determined by X-ray crystallography is not without standard error. For the purpose of this invention, any set of structure coordinates for a plant peptide deformylse from any source having a root mean square deviation (r.m.s.d) of non-hydrogen atoms of less than about 1.5 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1 are considered substantially identical or homologous. Moreover, any set of structure coordinates for plant peptide deformylse from any source having a root mean square deviation of non-hydrogen atoms of less than about 0.75 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1 are considered substantially identical or homologous.

The term “root mean square deviation” means the square root of the arithmetic mean of the squares of the deviations. It is a way to express the deviation or variation from a trend or object. For purposes of this invention, the “root mean square deviation” defines the variation in the backbone of a protein from the backbone of a Arabidopsis thaliana peptide deformylase polypeptide or an active site portion thereof, as defined by the structure coordinates described herein. “Having substantially the same three-dimensional structure” refers to a polypeptide that is characterized by a set of atomic structure coordinates that have a root mean square deviation (r.m.s.d.) of less than or equal to about 1.5 Å when superimposed onto the atomic structure coordinates of Table 1 when at least about 50% to 100% of the C α atoms of the coordinates are included in the superposition.

Slight variations in structure coordinates can be generated by mathematically manipulating the plant peptide deformylase structure coordinates provided herein. For example, the structure coordinates set forth in Table 1 could be manipulated by crystallographic permutations of the structure coordinates, fractionalization of the structure coordinates, integer additions or subtractions to sets of the structure coordinates, inversion of the structure coordinates or any combination of the above. Alternatively, modifications in the crystal structure due to mutations, additions, substitutions, and/or deletions of amino acids, or other changes in any of the components that make up the crystal, could also yield variations in structure coordinates. Such slight variations in the individual coordinates will have little effect on overall shape. If such variations are within an acceptable standard error as compared to the original coordinates, the resulting three-dimensional shape is considered to be structurally equivalent. Thus, for the purpose of the structures provided herein, any active site, binding site or binding pocket defined by a set of structure coordinates for a polypeptide or for a homolog of a polypeptide from any source having a root mean square deviation of non-hydrogen atoms of less than about 1.5 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table 1, are considered substantially identical or homologous.

Active sites are of significant utility in the identification of compounds that specifically interact with, and modulate the activity of, a particular polypeptide. The association of natural ligands or substrates with the active sites of their corresponding receptors or enzymes is the basis of many biological mechanisms of action. Similarly, many compounds exert their biological effects through association with the active sites of receptors and enzymes. Such associations may occur with all or any parts of the active site. An understanding of such associations helps lead to the design of compounds that modulate the activity of their target. Therefore, this information is valuable in designing potential modifiers of plant peptide deformylase activity, as discussed in more detail below. For example, the structure of a substrate utilized by a particular deformylase can be used to design compounds that bind to an active site of a peptide deformylase. Referring to FIG. 3, substrate specificities for plant peptide deformylase AtDEF1 and AtDEF2 are shown. AtDEF1 and 2 activities are influenced by peptide substrate sequence. Peptide mimics of the N-termini of chloroplast-translated proteins, ribosomal protein S18 (f-MDKS), Rubisco LS (f-MSPQ), D1 (f-MTAI), PSI-I (f-MTTF), PSII-I (f-MLTL), and ATPase subunit III (f-MNPL) were tested as substrates. In addition to a control substrate for the assay (f-MAS), the formate-dehydrogenase-linked assay was performed with 4 mM substrate and either 1.2 mg AtDEF1 or 0.2 mg AtDEF2. The numbers above the grouped bars represent the ratio of AtDEF2 to AtDEF1 activities. (Dirk et al., Arch Biochem Biophys 406:135-141).

The term “active site (or binding pocket),” as used herein, refers to a region of a molecule or molecular complex, that, as a result of its shape, favorably associates with another chemical entity or compound. Thus, an active site may include or consist of features such as interfaces between domains. Chemical entities or compounds that may associate with an active site include, but are not limited to, compounds, ligands, cofactors, substrates, inhibitors, agonists, antagonists, etc.

An exemplary active site for a plant peptide deformylase is provided by amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 of SEQ ID NO:1 and as shown in Table 1. Referring to FIG. 5, a model of the D1 N-terminus in AtDEF2's active site is provided. Potential H-bond highlighted between the Thr in the P₂ position of the polypeptide substrate and a conserved AtDEF2 Tyr178 just carboxy terminal to motif II. The model was generated by taking a snapshot from a molecular dynamics simulation using AMBER. The total length of the simulation was 1 ns, and this snapshot is at 126 ps.

In general, the exemplary active site is defined by a set of points having a root mean square deviation of less than about 0.35 Å from points representing the backbone atoms of amino acids as represented by structure coordinates listed in Table 1. As noted above, the crystalline form optionally includes additional molecules such as a coordinated metal ion selected from the group of metals consisting of Fe, Zn, Ni and combinations thereof. In some aspects, the metal ion is coordinated by the amino acids Cys171, His213, and His217.

Also provided are scalable three-dimensional configuration of points, at least a portion of said points derived from structure coordinates of at least a portion of an Arabidopsis thaliana peptide deformylase molecule or molecular complex listed in Table 1 and having a root mean square deviation of about 1.04 Å from said structure coordinates. Preferably, at least a portion of the points are derived from the Arabidopsis thaliana peptide deformylase structure coordinates derived from structure coordinates representing the locations of at least the backbone atoms of a plurality of the amino acids defining at least one Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site, the active site including amino acids Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178.

The structure coordinates generated for a plant peptide deformylase, or an active site thereof, as shown in Table 1 define a unique configuration of points in space. Those of skill in the art understand that a set of structure coordinates for a polypeptide, or a polypeptide complexed with a chemical entity, or a portion thereof, define a relative set of points that, in turn, define a configuration in three dimensions. A similar or identical configuration can be defined by an entirely different set of coordinates, provided the distances and angles between coordinates remain essentially the same. Accordingly, the coordinates provided in Table 1 provide a “scalable” configuration of points that can be modified by increasing or decreasing the distances between coordinates by a scalar factor while keeping the angles essentially the same.

The atomic structure coordinates provided herein can be used in molecular modeling and design, as described more fully below. The present invention encompasses the structure coordinates and other information, e.g., amino acid sequence, connectivity tables, vector-based representations, temperature factors, etc., used to generate the three-dimensional structure of the plant peptide deformylase polypeptide for use in the software programs described below and other software programs.

The invention encompasses machine-readable media embedded with the three-dimensional structure of the model described herein, or with portions thereof. As used herein, “machine-readable medium” refers to any medium that can be read and accessed directly by a computer or scanner. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium and magnetic tape; optical storage media such as optical discs or CD-ROM; electrical storage media such as RAM or ROM; and hybrids of these categories such as magnetic/optical storage media. Such media further include paper on which is recorded a representation of the atomic structure coordinates, e.g., Cartesian coordinates, that can be read by a scanning device and converted into a three-dimensional structure with an OCR.

A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon the atomic structure coordinates of the invention or portions thereof and/or X-ray diffraction data. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the sequence and X-ray data information on a computer readable medium. Such formats include, but are not limited to, Protein Data Bank (“PDB”) format (Research Collaboratory for Structural Bioinformatics; Cambridge Crystallographic Data Centre format; Structure-data (“SD”) file format (MDL Information Systems, Inc.; Dalby et al., 1992, J. Chem. Inf. Comp. Sci. 32:244-255), and line-notation, e.g., as used in SMILES (Weininger, 1988, J. Chem. Inf. Comp. Sci. 28:31-36). Methods of converting between various formats read by different computer software will be readily apparent to those of skill in the art, e.g., BABEL (v. 1.06, Walters & Stahl, .COPYRGT. 1992, 1993, 1994). All format representations of the polypeptide coordinates described herein, or portions thereof, are contemplated by the present invention. By providing computer readable medium having stored thereon the atomic coordinates of the invention, one of skill in the art can routinely access the atomic coordinates of the invention, or portions thereof, and related information for use in modeling and design programs, described in detail below.

While Cartesian coordinates are important and convenient representations of the three-dimensional structure of a polypeptide, those of skill in the art will readily recognize that other representations of the structure are also useful. Therefore, the three-dimensional structure of a polypeptide, as discussed herein, includes not only the Cartesian coordinate representation, but also all alternative representations of the three-dimensional distribution of atoms. For example, atomic coordinates may be represented as a Z-matrix, wherein a first atom of the protein is chosen, a second atom is placed at a defined distance from the first atom, a third atom is placed at a defined distance from the second atom so that it makes a defined angle with the first atom. Each subsequent atom is placed at a defined distance from a previously placed atom with a specified angle with respect to the third atom, and at a specified torsion angle with respect to a fourth atom. Atomic coordinates may also be represented as a Patterson function, wherein all interatomic vectors are drawn and are then placed with their tails at the origin. This representation is particularly useful for locating heavy atoms in a unit cell. In addition, atomic coordinates may be represented as a series of vectors having magnitude and direction and drawn from a chosen origin to each atom in the polypeptide structure. Furthermore, the positions of atoms in a three-dimensional structure may be represented as fractions of the unit cell (fractional coordinates), or in spherical polar coordinates.

Additional information, such as thermal parameters, which measure the motion of each atom in the structure, chain identifiers, which identify the particular chain of a multi-chain protein in which an atom is located, and connectivity information, which indicates to which atoms a particular atom is bonded, is also useful for representing a three-dimensional molecular structure.

Accordingly, also provided herein is a machine-readable data storage medium including a data storage material encoded with machine readable data which, when using a machine programmed with instructions for using the data, displays a graphical three-dimensional representation of at least one molecule or molecular complex selected from the group consisting of (i) a molecule or molecular complex including at least a portion of an Arabidopsis thaliana peptide deformylase or an Arabidopsis thaliana peptide deformylase-like active site including amino acids Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 the active site being defined by a set of points having a root mean square deviation of less than about 1.5 Å from points representing the backbone atoms of the amino acids as represented by structure coordinates listed in Table 1.

Structure information, typically in the form of the atomic structure coordinates, can be used in a variety of computational or computer-based methods to, for example, design, screen for and/or identify compounds that bind the crystallized polypeptide or a portion or fragment thereof, or to intelligently design mutants that have altered biological properties, and the like. Three-dimensional modeling may be performed using the experimentally determined coordinates derived from X-ray diffraction patterns, such as those in Table 1, for example, wherein such modeling includes, but is not limited to, drawing pictures of the actual structures, building physical models of the actual structures, and determining the structures of related subunits and /ligand and subunit/ligand complexes using the coordinates. Such molecular modeling can utilize known X-ray diffraction molecular modeling algorithms or molecular modeling software to generate atomic coordinates corresponding to the three-dimensional structure of a plant peptide deformylase.

As described above, molecular modeling involves the use of computational methods, preferably computer assisted methods, to build realistic models of molecules that are identifiably related in sequence to the known crystal structure. It also involves modeling new small molecule inhibitors bound to a plant peptide deformylase starting with the structures of deformylase alone or complexed with known ligands or inhibitors. The methods utilized in ligand modeling range from molecular graphics (i.e., 3D representations) to computational chemistry (i.e., calculations of the physical and chemical properties) to make predictions about the binding of ligands or activities of ligands; to design new ligands; and to predict novel molecules, including ligands such as compounds that inhibit the activity of a plant deformylase. Such compounds may be useful as herbicides, for example.

One approach to rational design of a compound is to search for known molecular structures that might bind to an active site. Using molecular modeling, rational design programs can look at a range of different molecular structures of compounds that may fit into the active site of an enzyme or protein, and by moving them in a three-dimensional environment it can be decided which structures actually fit the site well. An alternate but related rational compound design approach starts with the known structure of a complex with a small molecule ligand and models modifications of that small molecule in an effort to make additional favorable interactions with peptide deformylase polypeptides, and/or the active site of such polypeptides.

The present invention includes the use of molecular and computer modeling techniques to design and select ligands, such as small molecule agonists or antagonists or other compounds that interact with peptide deformylase polypeptides. Such compounds include, but are not limited to, actinonin and derivatives thereof.

This invention also includes the design of compounds that act as uncompetitive inhibitors of at least one function of peptide deformylase polypeptides. These inhibitors may bind to all, or a portion of, the active sites or other regions of the polypeptide already bound to a ligand and may be more potent and less non-specific than competitive inhibitors that compete for active sites. Similarly, non-competitive inhibitors that bind to and inhibit at least one function of peptide deformylase polypeptides whether or not it is bound to another chemical entity, such as a natural ligand, for example, may be designed using the atomic coordinates of the chimeras or complexes comprising the chimeras of this invention.

The atomic coordinates of the present invention also provide the needed information to probe a crystal of a peptide deformylase polypeptide with molecules composed of a variety of different chemical features to determine optimal sites for interaction between candidate inhibitors and/or activators. For example, high resolution X-ray diffraction data collected from crystals saturated with solvent allows the determination of where each type of solvent molecule sticks. Small molecules that bind to those sites can then be designed and synthesized and tested for their inhibitory activity (Travis, J., Science 262:1374 (1993)).

The present invention also includes methods for computationally screening small molecule databases and libraries for chemical entities, agents, ligands, or compounds that can bind in whole, or in part, to peptide deformylase polypeptides. In this screening, the quality of fit of such entities or compounds to the binding site or sites may be judged either by shape complementarity or by estimated interaction energy (Meng, E. C. et al., J. Comp. Chem. 13:505-524 (1992)).

The design of compounds that bind to, promote or inhibit the functional activity of peptide deformylase polypeptides according to this invention generally involves consideration of two factors. First, the compound must be capable of physically and structurally associating with the peptide deformylase polypeptide. Non-covalent molecular interactions important in the association of the peptide deformylase polypeptide with the compound include hydrogen bonding, van der Waals and hydrophobic interactions. Second, the compound must be able to assume a conformation that allows it to associate with a peptide deformylase polypeptide. Although certain portions of the compound may not directly participate in the association with peptide deformylase polypeptide, those portions may still influence the overall conformation of the molecule. This, in turn, may have a significant impact on binding affinities and potency. Such conformational requirements include the overall three-dimensional structure and orientation of the chemical entity or compound in relation to all or a portion of the active site or other region of a peptide deformylase polypeptide, or the spacing between functional groups of a compound comprising several chemical entities that directly interact with a peptide deformylase polypeptide.

The potential, predicted, inhibitory agonist, antagonist or binding effect of a ligand or other compound on a peptide deformylase polypeptide may be analyzed prior to its actual synthesis and testing by the use of computer modeling techniques. If the theoretical structure of the given compound suggests insufficient interaction and association between it and the peptide deformylase polypeptide, synthesis and testing of the compound may be obviated. However, if computer modeling indicates a strong interaction, the molecule may then be synthesized and tested for its ability to interact with a peptide deformylase polypeptide. In this manner, synthesis of inoperative compounds may be avoided. In some cases, inactive compounds are synthesized predicted on modeling and then tested to develop a SAR (structure-activity relationship) for compounds interacting with a specific region of a peptide deformylase polypeptide.

One skilled in the art may use one of several methods to screen chemical entities fragments, compounds, or agents for their ability to associate with a peptide deformylase polypeptide and more particularly with the individual binding pockets or active sites of the peptide deformylase polypeptide. This process may begin by visual inspection of, for example, the active site based on the atomic coordinates of the polypeptide or the polypeptide complexed with a ligand. Selected chemical entities, compounds, or agents may then be positioned in a variety of orientations, or docked within an individual binding pocket of the peptide deformylase polypeptide. Docking may be accomplished using software-such as Quanta and Sybyl, followed by energy minimization and molecular dynamics with standard molecular mechanics forcefields, such as CHARMM and AMBER.

Specialized computer programs may also assist in the process of selecting chemical entities. These include but are not limited to: GRID (Goodford, P. J., “A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules,” J. Med. Chem. 28:849-857 (1985), available from Oxford University, Oxford, UK); MCSS (Miranker, A. and M. Karplus, “Functionality Maps of Binding Sites: A Multiple Copy Simultaneous Search Method.” Proteins: Structure, Function and Genetics 11: 29-34 (1991), available from Molecular Simulations, Burlington, Mass.); AUTODOCK (Goodsell, D. S, and A. J. Olsen, “Automated Docking of Substrates to Proteins by Simulated Annealing” Proteins: Structure. Function, and Genetics 8:195-202 (1990), available from Scripps Research Institute, La Jolla, Calif.); DOCK (Kuntz, I. D. et al., “A Geometric Approach to Macromolecule-Ligand Interactions,” J. Mol. Biol. 161:269-288 (1982), available from University of California, San Francisco, Calif.); Gold (Jones, G. et al., “Development and validation of a genetic algorithm for flexible docking.” J. Mol. Biol. 267: 727-748 (1997)); Glide (Halgren, T. A. et al., “Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening.” J Med Chem, 47:1750-1759 (2004), Friesner, R. A. et al., “Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy.” J Med Chem, 47:1739-1749 (2004)); FlexX (Rarey, M. et al., “A fast flexible docking method using an incremental construction algorithm.” J. Mol. Biol. 261: 470-489 (1996)); and ICM (Abagyan, R. A. and Totrov, M. M., J. Mol. Biol. 235: 983-1002 (1994)).

The use of software such as GRID, a program that determines probable interaction sites between probes with various functional group characteristics and the macromolecular surface, is used to analyze the surface sites to determine structures of similar inhibiting proteins or compounds. The GRID calculations, with suitable inhibiting groups on molecules (e.g., protonated primary amines) as the probe, are used to identify potential hotspots around accessible positions at suitable energy contour levels. The program DOCK may be used to analyze an active site or ligand binding site and suggest ligands with complementary steric properties. See also, See, also, Kellenberger, P. N et al., “Recovering the true targets of specific ligands by virtual screening of the protein data bank,” Proteins 54(4):671-80 (2004); Oldfield, T., “Applications for macromolecular map interpretation: X-AUTOFIT, X-POWERFIT, X-BUILD, X-LIGAND, and X-SOLVATE,” Methods Enzymol. 374:271-300 (2003); Richardson, J. S. et al., “New tools and data for improving structures, using all-atom contacts,” Methods Enzymol. 374: 385-412 (2003); Terwilliger, T. C., “Improving macromolecular atomic models at moderate resolution by automated iterative model building, statistical density modification and refinement,” Acta Crystallogr D Biol Crystallogr. 59(Pt 7): 1174-82 (2003); Toerger, T. C. and Sacchettini, J. C., “TEXTAL system: artificial intelligence techniques for automated protein model building,” Methods Enzymol. 374:244-70 (2003); von Grotthuss, M. et al., “Predicting protein structures accurately,” Science 304(5677):1597-9 (2004); Rajakiannan, V. et al., “The use of ACORN in solving a 39.5 kDa macromolecule with 1.9 Å resolution laboratory source data,” J Synchrotron Radiat. 11(Pt 4):358-62 (2004); Claude, J. B. et al., “CaspR: a web server for automated molecular replacement using homology modeling,” Nucleic Acids Res. 32(Web Server issue):W606-9 (2004); Suhre, K. and Sanejouand, Y. H., “ElNemo: a normal mode web server for protein movement analysis and the generation of templates for molecular replacement,” Nucleic Acids Res. 32(Web Server issue):W610-4 (2004).

Once suitable chemical entities, compounds, or agents have been selected, they can be assembled into a single ligand or compound or inhibitor or activator. Assembly may proceed by visual inspection of the relationship of the fragments to each other on the three-dimensional image. This may be followed by manual model building using software such as Quanta or Sybyl.

Useful programs to aid in connecting the individual chemical entities, compounds, or agents include but are not limited to: CAVEAT (Bartlett, P. A. et al., “CAVEAT: A Program to Facilitate the Structure-Derived Design of Biologically Active Molecules.” In Molecular Recognition in Chemical and Biological, Problems, Special Pub., Royal Chem. Soc., 78, pp. 82-196 (1989)); 3D Database systems such as MACCS-3D (MDL Information Systems, San Leandro, C A and Martin, Y. C., “3D Database Searching in Drug Design,” J. Med. Chem. 35: 2145-2154 (1992); and HOOK (available from Molecular Simulations, Burlington, Mass.).

Several methodologies for searching three-dimensional databases to test hypotheses and select compounds for screening are available. These include the program CAVEAT (Bacon et al., J. Mol. Biol. 225:849-858 (1992)). For instance, CAVEAT uses databases of cyclic compounds which can act as “spacers” to connect any number of chemical fragments already positioned in the active site. This allows one skilled in the art to quickly generate hundreds of possible ways to connect the fragments already known or suspected to be necessary for tight binding.

Instead of proceeding to build an inhibitor activator, agonist or antagonist of a peptide deformylase polypeptide in a step-wise fashion one chemical entity at a time as described above, such compounds may be designed as a whole or “de novo” using either an empty active site or optionally including some portion(s) of a known molecules. These methods include: LUDI (Bohm, H.-J., “The Computer Program LUDI: A New Method for the De Novo Design of Enzyme Inhibitors”, J. Comp. Aid. Molec. Design, 6, pp. 61-78 (1992), available from Biosym Technologies, San Diego, Calif.); LEGEND (Nishibata, Y. and A. Itai, Tetrahedron 47:8985 (1991), available from Molecular Simulations, Burlington, Mass.); and LeapFrog (available from Tripos Associates, St. Louis, Mo.).

For instance, the program LUDI can determine a list of interaction sites into which to place both hydrogen bonding and hydrophobic fragments. LUDI then uses a library of linkers to connect up to four different interaction sites into fragments. Then smaller “bridging” groups such as —CH2- and —COO— are used to connect these fragments.

Once a compound has been designed or selected by the above methods, the affinity with which that compound may bind or associate with a peptide deformylase polypeptide may be tested and optimized by computational evaluation and/or by testing biological activity after synthesizing the compound. Inhibitors or compounds may interact with the deformylase in more than one conformation that is similar in overall binding energy. In those cases, the deformation energy of binding is taken to be the difference between the energy of the free compound and the average energy of the conformations observed when the compound binds to a peptide deformylase polypeptide.

A compound designed or selected as binding or associating with a plant peptide deformylase may be further computationally optimized so that in its bound state it would preferably lack repulsive electrostatic interaction with the protein. Such non-complementary (e.g., electrostatic) interactions include repulsive charge-charge, dipole-dipole and charge-dipole interactions. Specifically, the sum of all electrostatic interactions between the inhibitor and the chimera when the inhibitor is bound, preferably make a neutral or favorable contribution to the enthalpy of binding. Weak binding compounds will also be designed by these methods so as to determine SAR.

Specific computer software is available in the art to evaluate compound deformation energy and electrostatic interaction. Examples of programs designed for such uses include: Gaussian 92, revision C (M. J. Frisch, Gaussian, Inc., Pittsburgh, Pa., COPYRGT 1992); AMBER, version 4.0 (P. A. Kollman, University of California at San Francisco, COPYRGT 1994); QUANTA/CHARMM (Molecular Simulations, Inc., Burlington, Mass. COPYRGT 1994); INSIGHT II/DISCOVER (Biosysm Technologies Inc., San Diego, Calif. COPYRGT. 1994); and DELPHI (A. Nicholls and B. Honig “A rapid finite difference algorithm, utilizing successive over-relaxation to solve the Poisson-Boltzman equation” J. Comp. Chem. 12: 435-445 (1991), M. K. Gilson and B. Honig. “Calculation of the total electrostatic energy of a macromolecular system: Solvation energies, binding energies and conformation analysis” Proteins 4: 7-18 (1988), M. K. Gilson et al., “Calculating the electrostatic potential of molecules in solution: Method and error assessment” J. Comp. Chem. 9: 327-335 (1987)). Other hardware systems and software packages will be known to those skilled in the art.

Once a compound that associates with the peptide deformylase polypeptide has been optimally selected or designed, as described above, substitutions may then be made in some of its atoms or side groups in order to improve or modify its binding properties. Generally, initial substitutions are conservative, i.e., the replacement group will have approximately the same size, shape, hydrophobicity and charge as the original group. It should, of course, be understood that components known in the art to alter conformation may be avoided. Such substituted chemical compounds may then be analyzed for efficiency of fit to a peptide deformylase polypeptide by the same computer methods described in detail, above.

Accordingly, as described above the present invention provides a computer-assisted method for obtaining structural information about a molecule or a molecular complex of unknown structure including: crystallizing the molecule or molecular complex; generating an x-ray diffraction pattern from the crystallized molecule or molecular complex; applying at least a portion of the structure coordinates set forth in Table 1 to the x-ray diffraction pattern to generate a three-dimensional electron density map of at least a portion of the molecule or molecular complex whose structure is unknown.

In another aspect, the present invention provides a computer-assisted method for homology modeling an Arabidopsis thaliana peptide deformylase homolog including: aligning the amino acid sequence of an Arabidopsis thaliana peptide deformylase homolog with the amino acid sequence of Arabidopsis thaliana peptide deformylase SEQ ID NO:1 and incorporating the sequence of the Arabidopsis thaliana peptide deformylase homolog into a model of Arabidopsis thaliana peptide deformylase derived from structure coordinates set forth in Table 1 to yield a preliminary model of the Arabidopsis thaliana peptide deformylase homolog; subjecting the preliminary model to energy minimization to yield an energy minimized model; remodeling regions of the energy minimized model where stereochemistry restraints are violated to yield a final model of the Arabidopsis thaliana peptide deformylase homolog.

Domains of peptide deformylase polypeptides retain sequence and structural conservation. Accordingly, these conserved regions can be used to model deformylase homologs. Referring to FIG. 4, conservation of the three motifs in AtDEF1 and 2 and bacterial DEFs are shown. AtDEF1- and 2-like sequences were identified with a tblastn (BLAST) search of plant EST databases, aligned around the indicated motifs, and submitted for analysis by WebLogo. For the bacterial DEF alignment, the first 100 bacterial sequences from a blastp using the SwissProt database with Q2VP16 (E. coli) as query were used for the similarity analyses. Sequence conservation is represented by WebLogo images by the overall height of the stack and relative frequency of the amino acid at the position within the sequence is represented by the height of its symbol (Crooks et al., Genome Res. 14:1188-1190; Schneider and Stephens, Nucl. Acids Res. 18:6097-6100).

Due to the nature of the sequences used for the plant DEFs, different numbers of sequences were used for each motif in the generation of FIG. 4. For motif I, there were 34, 42 and 100 sequences for 1, 2 and bacterial DEFs, respectively; whereas, there were 36, 40, and 100 for motif II and 40, 32, and 100 for motif II.

In addition, referring to FIGS. 6, 7 and 8, a phylogenetic analyses of the distribution of amino acid substitutions throughout the available collection of peptide deformylase sequences from plants compared with bacterial deformylase is provided. The results are presented as a comparison of both the number and percentage of substitutions found at any location within the sequence of peptide deformylase 1 & 2 from plants as well as E. coli. There are a number of residue changes which suggest selection pressure in the evolution of peptide deformylase specifically adapted to plants. Thus, these changes are indicative of specific sites where residue changes are likely to affect peptide deformylase activity and/or specificity without adversely affecting enzyme stability and are useful as targets for mutational changes.

Thus, the structure coordinates set forth in Table 1 can be used to aid in obtaining structural information about another crystallized molecule or molecular complex. A “molecular complex” means a protein in covalent or non-covalent association with a chemical entity or compound. The method of the invention allows determination of at least a portion of the three-dimensional structure of molecules or molecular complexes which contain one or more structural features that are similar to structural features of Arabidopsis thaliana peptide deformylase. These molecules are referred to herein as “structurally homologous” to Arabidopsis thaliana peptide deformylase. Similar structural features can include, for example, regions of amino acid identity, conserved active site or binding site motifs, and similarly arranged secondary structural elements (e.g., α helices and β sheets). Optionally, structural homology is determined by aligning the residues of the two amino acid sequences to optimize the number of identical amino acids along the lengths of their sequences; gaps in either or both sequences are permitted in making the alignment in order to optimize the number of identical amino acids, although the amino acids in each sequence must nonetheless remain in their proper order. Preferably, two amino acid sequences are compared using the Blastp program, version 2.0.9, of the BLAST 2 search algorithm, as described by Tatusova et al., FEMS Microbiol Lett., 174:247-50 (1999). Preferably, the default values for all BLAST 2 search parameters are used, including matrix=BLOSUM62; open gap penalty=11, extension gap penalty=1, gap x_dropoff=50, expect=10, wordsize=3, and filter on. In the comparison of two amino acid sequences using the BLAST search algorithm, structural similarity is referred to as “identity.” Preferably, a structurally homologous molecule is a protein that has an amino acid sequence sharing at least 65% identity with the amino acid sequence of Arabidopsis thaliana peptide deformylase. Methods for generating structural information about the structurally homologous molecule or molecular complex are well-known and include, for example, molecular replacement techniques. By using molecular replacement, all or part of the structure coordinates of Arabidopsis thaliana peptide deformylase (and set forth in Table 1) can be used to determine the structure of a crystallized molecule or molecular complex whose structure is unknown more quickly and efficiently than attempting to determine such information ab initio.

Molecular replacement provides an accurate estimation of the phases for an unknown structure. Phases are a factor in equations used to solve crystal structures that cannot be determined directly. Obtaining accurate values for the phases, by methods other than molecular replacement, is a time-consuming process that involves iterative cycles of approximations and refinements and greatly hinders the solution of crystal structures. However, when the crystal structure of a protein containing at least a structurally homologous portion has been solved, the phases from the known structure provide a satisfactory estimate of the phases for the unknown structure.

Thus, this method involves generating a preliminary model of a molecule or molecular complex whose structure coordinates are unknown, by orienting and positioning the relevant portion of Arabidopsis thaliana peptide deformylase according to Table 1 within the unit cell of the crystal of the unknown molecule or molecular complex so as best to account for the observed x-ray diffraction pattern of the crystal of the molecule or molecular complex whose structure is unknown. Phases can then be calculated from this model and combined with the observed x-ray diffraction pattern amplitudes to generate an electron density map of the structure whose coordinates are unknown. This, in turn, can be subjected to any well-known model building and structure refinement techniques to provide a final, accurate structure of the unknown crystallized molecule or molecular complex (E. Lattman, “Use of the Rotation and Translation Functions,” in Meth. Enzymol., 115:55-77 (1985); M. G. Rossman, ed., “The Molecular Replacement Method,” Int. Sci. Rev. Ser., No. 13, Gordon & Breach, New York (1972)).

Structural information about a portion of any crystallized molecule or molecular complex that is sufficiently structurally homologous to a portion of Arabidopsis thaliana peptide deformylase can be resolved by this method. In addition to a molecule that shares one or more structural features with Arabidopsis thaliana peptide deformylase as described above, a molecule that has similar bioactivity, such as the same catalytic activity, substrate specificity or ligand binding activity as Arabidopsis thaliana peptide deformylase, may also be sufficiently structurally homologous to Arabidopsis thaliana peptide deformylase to permit use of the structure coordinates of Arabidopsis thaliana peptide deformylase to solve its crystal structure.

In addition, using homology modeling, a computer model of an Arabidopsis thaliana peptide deformylase homolog can be built or refined without crystallizing the homolog. First, a preliminary model of the Arabidopsis thaliana peptide deformylase homolog is created by sequence alignment with Arabidopsis thaliana peptide deformylase, secondary structure prediction, the screening of structural libraries, or any combination of those techniques. Computational software may be used to carry out the sequence alignments and the secondary structure predictions. Structural incoherences, e.g., structural fragments around insertions and deletions, can be modeled by screening a structural library for peptides of the desired length and with a suitable conformation. For prediction of the side chain conformation, a side chain rotamer library may be employed. Where the Arabidopsis thaliana peptide deformylase homolog has been crystallized, the final homology model can be used to solve the crystal structure of the homolog by molecular replacement, as described above. Next, the preliminary model is subjected to energy minimization to yield an energy minimized model. The energy minimized model may contain regions where stereochemistry restraints are violated, in which case such regions are remodeled to obtain a final homology model. The homology model is positioned according to the results of molecular replacement, and subjected to further refinement including molecular dynamics calculations.

In another aspect, the present invention provides a computer-assisted method for designing a potential modifier of Arabidopsis thaliana peptide deformylase activity including: supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of at least one Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site, the active site including amino acids Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His 217, and Tyr178; supplying the computer modeling application with a set of structure coordinates for a chemical entity; evaluating the potential binding interactions between the chemical entity and active site of the molecule or molecular complex; structurally modifying the chemical entity to yield a set of structure coordinates for a modified chemical entity; and determining whether the modified chemical entity is expected to bind to the molecule or molecular complex, wherein binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.

The present invention also provides a computer-assisted method for designing a potential modifier of Arabidopsis thaliana peptide deformylase activity de novo including: supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of at least one Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase like active site, wherein the active site includes amino acids Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178; forming a chemical entity represented by set of structure coordinates; and determining whether the chemical entity is expected to bind to the molecule or molecular complex, wherein binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.

In another aspect, the present invention provides a method for making a potential modifier of Arabidopsis thaliana peptide deformylase activity, the method including chemically or enzymatically synthesizing a chemical entity to yield a potential modifier of Arabidopsis thaliana peptide deformylase activity, the chemical entity having been identified during a computer-assisted process including supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of a Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site; supplying the computer modeling application with a set of structure coordinates of a chemical entity; and determining whether the chemical entity is expected to bind to the molecule or molecular complex at the active site, wherein binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.

In another aspect, the present invention provides a method for making a potential modifier of Arabidopsis thaliana peptide deformylase activity, the method including chemically or enzymatically synthesizing a chemical entity to yield a potential modifier of Arabidopsis thaliana peptide deformylase activity, the chemical entity having been designed during a computer-assisted process including supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of a Arabidopsis thaliana peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site; supplying the computer modeling application with a set of structure coordinates for a chemical entity; evaluating the potential binding interactions between the chemical entity and the active site of the molecule or molecular complex; structurally modifying the chemical entity to yield a set of structure coordinates for a modified chemical entity; and determining whether the chemical entity is expected to bind to the molecule or molecular complex at the active site, wherein binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.

In general, methods for making a potential modifier of a plant peptide deformylase activity are provided herein. Such methods include chemically or enzymatically synthesizing a chemical entity to yield a potential modifier of plant peptide deformylase activity. Those skilled in the art of crystallography will understand that the atomic coordinates provided herein can be used to design a chemical entity during a computer-assisted process that includes supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex, the molecule or molecular complex including at least a portion of a plant peptide deformylase or Arabidopsis thaliana peptide deformylase-like active site; forming a chemical entity represented by set of structure coordinates; and determining whether the chemical entity is expected to bind to the molecule or molecular complex at the active site. Binding to the molecule or molecular complex is indicative of potential modification of Arabidopsis thaliana peptide deformylase activity.

FIGS. 6-8 contain phylogenetic analyses of the distribution of amino acid substitutions throughout the available collection of peptide deformylase sequences from plants compared with bacteria. The results are presented as a comparison of both the number and percentage of substitutions found at any location within the sequence of peptide deformylase 1 & 2 from plants as well as E. coli. There are a number of residue changes which suggest selection pressure in the evolution of peptide deformylase specifically adapted to plants. Thus, these changes are indicative of specific sites where residue changes are likely to affect peptide deformylase activity and/or specificity without adversely affecting enzyme stability and are useful as targets for mutational changes.

AtDEF2 is an essential plant enzyme responsible for the co-translational processing of chloroplast translated proteins. Although biochemically characterized, no structure exists for AtDEF2 in part because of a requirement for 0.5 M NaCl for solubility. The dependency on sodium chloride for solubility was removed by limited tryptic proteolysis and crystals of AtDEF2 were obtained. The structure was determined by molecular replacement and refined to a resolution of 2.7 Å. The overall fold of the enzyme closely resembles the alpha+beta conformation of known bacterial peptide deformylases, with an r.m.s deviation of 1.04 Å on main chain atoms relative to the E. coli enzyme. The largest differences occur in the orientation of the C-terminal helix (helix 3) and the conformation of the loop between beta strands 2 and 3, which form part of the five-stranded central sheet. Modeling the preferred substrate for AtDEF2 (the N-termini of the D1 polypeptide from photosystem II), in both chloroplast protein structures can be used to elucidate the mechanism underlying the 102-fold greater activity of AtDEF2 on this sequence (see FIG. 3). Structural comparison can also be accomplished with the known eubacterial peptide deformylase structures to determine approaches for designing specific inhibitors against the chloroplast enzyme. Specific AtDEF2 inhibitors could potentially be used as broad-spectrum herbicides without impact on soil microorganisms.

The Arabidopsis thaliana DEF2 protein was over-expressed and purified from E. coli. Limited tryptic proteolysis yielded a form of Arabidopsis thaliana DEF2 (see FIG. 1B, SEQ ID NO:1) which readily crystallized. The useful crystals all belong to the tetragonal space group. The unit cell parameters were a, b, and c; wherein a is about 40 Å to about 60 Å, b is about 40 Å to about 60 Å, and c is about 120 Å to about 160 Å.

Crystals of the truncated peptide deformylase construct are grown by hanging drop vapor diffusion in 24 well plates with well solutions containing 15-18% peg monomethyl ester 550, 28-70 mM ZnSO₄, and 70 mM MES pH 6.5. Protein solution at approximately 5 mg/m¹ is mixed 1:1 with well solution to a final volume of 2-5 microliters for the crystallization drops. Crystals form in several days to several weeks. To prepare the crystals for data collection, they were briefly placed into a solution containing the same components as the well solution in addition to 20% glycerol, mounted in nylon or mylar loops, and flash cooled by plunging into liquid nitrogen.

Table 1 lists the atomic structure coordinates for the Arabidopsis thaliana peptide deformylase (A. thaliana DEF2) molecule as derived by x-ray diffraction from a crystal of the protein. The following abbreviations are used in Table 1. “Atom type” refers to the element whose coordinates are measured. The first letter in the column defines the element. “X, Y, Z” crystallographically define the atomic position of the element measured. “B” is a thermal factor that measures movement of the atom around its atomic center. “Occ” is an occupancy factor that refers to the fraction of the molecules in which each atom occupies the position specified by the coordinates. A value of “1” indicates that each atom has the same conformation, i.e., the same position, in all molecules of the crystal.

Table 1 is provided below:

TABLE 1 Atomic Coordinates of Crystalline Form of SEQ ID NO: 1 REMARK coordinates from simulated annealing refinement REMARK refinement resolution: 500.0-2.4 A REMARK starting r = 0.2407 free_r = 0.2946 REMARK final r = 0.2352 free_r = 0.2983 REMARK rmsd bonds = 0.007053 rmsd angles = 1.33915 REMARK wa_initial = 2.77981 wa_dynamics = 3.30373 wa_final = 2.90342 REMARK target = mlf md-method = torsion annealing schedule = slowcool REMARK starting temperature = 2500 total md steps = 100 * 6 REMARK sg = P4(1)2(1)2 a = 50.902 b = 50.902 c = 144.783 alpha = 90 beta = 90 gamma = 90 REMARK parameter file 1  :  CNS_TOPPAR:protein_rep_cis.param REMARK parameter file 2  :  CNS_TOPPAR:ion.param REMARK parameter file 3  :  CNS_TOPPAR:water_rep.param REMARK molecular structure file: generate_r8h.mtf REMARK input coordinates: generate_r8h.pdb REMARK reflection file = pepdef1_p41212_cv.cns REMARK ncs = none REMARK B-correction resolution: 6.0-2.4 REMARK initial B-factor correction applied to fobs: REMARK  B11 =  1.447 B22 =  1.447 B33 =  −2.893 REMARK  B12 =  0.000 B13 =  0.000 B23 =   0.000 REMARK B-factor correction applied to coordinate array B:  1.092 REMARK bulk solvent: density level = 0.398841 e/A{circumflex over ( )}3, B-factor = 39.902 A{circumflex over ( )}2 REMARK reflections with |Fobs|/sigma_F < 0.0 rejected REMARK reflections with |Fobs| > 10000 * rms(Fobs) rejected REMARK theoretical total number of refl. in resol. range: 8021 (100.0%) REMARK number of unobserved reflections (no entry or |F| = 0):   5 (0.1%) REMARK number of reflections rejected:   0 (0.0%) REMARK total number of reflections used: 8016 (99.9%) REMARK number of reflections in working set: 7166 (89.3%) REMARK number of reflections in test set:  850 (10.6%) CRYST1  50.902  50.902  144.783  90.00  90.00  90.00 P 41 21 2 REMARK FILENAME = “anneal_pepdef1_r8h_1.pdb” REMARK DATE: 28-Apr-05 13:49:32 REMARK VERSION: 1.0 ATOM 1 CB ASP A 74 39.005 −3.139 −26.015 1.00 40.08 A ATOM 2 CG ASP A 74 37.793 −3.950 −25.591 1.00 39.52 A ATOM 3 OD1 ASP A 74 37.991 −5.048 −25.026 1.00 39.78 A ATOM 4 OD2 ASP A 74 36.651 −3.487 −25.804 1.00 37.24 A ATOM 5 C ASP A 74 39.677 −4.292 −28.136 1.00 39.44 A ATOM 6 O ASP A 74 38.789 −5.104 −28.382 1.00 40.59 A ATOM 7 N ASP A 74 41.403 −3.315 −26.608 1.00 40.71 A ATOM 8 CA ASP A 74 40.079 −3.996 −26.689 1.00 40.00 A ATOM 9 N VAL A 75 40.329 −3.631 −29.089 1.00 36.98 A ATOM 10 CA VAL A 75 40.043 −3.850 −30.503 1.00 34.57 A ATOM 11 CB VAL A 75 38.952 −2.881 −31.027 1.00 35.15 A ATOM 12 CG1 VAL A 75 37.610 −3.228 −30.407 1.00 35.82 A ATOM 13 CG2 VAL A 75 39.323 −1.440 −30.706 1.00 35.83 A ATOM 14 C VAL A 75 41.294 −3.686 −31.367 1.00 33.70 A ATOM 15 O VAL A 75 41.849 −2.591 −31.473 1.00 31.73 A ATOM 16 N GLN A 76 41.744 −4.785 −31.968 1.00 32.36 A ATOM 17 CA GLN A 76 42.917 −4.752 −32.834 1.00 31.43 A ATOM 18 CB GLN A 76 43.809 −5.977 −32.597 1.00 30.15 A ATOM 19 CG GLN A 76 43.948 −6.377 −31.146 1.00 32.55 A ATOM 20 CD GLN A 76 45.062 −7.391 −30.900 1.00 33.57 A ATOM 21 OE1 GLN A 76 45.222 −8.363 −31.647 1.00 30.76 A ATOM 22 NE2 GLN A 76 45.832 −7.169 −29.835 1.00 32.62 A ATOM 23 C GLN A 76 42.442 −4.747 −34.284 1.00 30.41 A ATOM 24 O GLN A 76 41.713 −5.642 −34.714 1.00 32.15 A ATOM 25 N PHE A 77 42.843 −3.737 −35.042 1.00 29.07 A ATOM 26 CA PHE A 77 42.442 −3.672 −36.437 1.00 29.03 A ATOM 27 CB PHE A 77 41.147 −2.871 −36.582 1.00 26.50 A ATOM 28 CG PHE A 77 41.287 −1.426 −36.198 1.00 25.67 A ATOM 29 CD1 PHE A 77 41.416 −0.442 −37.172 1.00 25.19 A ATOM 30 CD2 PHE A 77 41.317 −1.050 −34.858 1.00 24.82 A ATOM 31 CE1 PHE A 77 41.572 0.895 −36.818 1.00 23.61 A ATOM 32 CE2 PHE A 77 41.473 0.283 −34.497 1.00 24.11 A ATOM 33 CZ PHE A 77 41.600 1.258 −35.483 1.00 23.48 A ATOM 34 C PHE A 77 43.523 −3.035 −37.287 1.00 30.55 A ATOM 35 O PHE A 77 44.372 −2.293 −36.789 1.00 28.47 A ATOM 36 N GLU A 78 43.487 −3.355 −38.576 1.00 33.02 A ATOM 37 CA GLU A 78 44.418 −2.797 −39.542 1.00 34.82 A ATOM 38 CB GLU A 78 44.965 −3.876 −40.491 1.00 35.56 A ATOM 39 CG GLU A 78 45.913 −4.906 −39.860 1.00 35.90 A ATOM 40 CD GLU A 78 45.187 −5.934 −39.001 1.00 37.85 A ATOM 41 OE1 GLU A 78 44.210 −6.534 −39.493 1.00 39.60 A ATOM 42 OE2 GLU A 78 45.590 −6.152 −37.841 1.00 37.63 A ATOM 43 C GLU A 78 43.580 −1.814 −40.339 1.00 35.67 A ATOM 44 O GLU A 78 42.386 −2.030 −40.543 1.00 34.84 A ATOM 45 N THR A 79 44.184 −0.713 −40.755 1.00 36.81 A ATOM 46 CA THR A 79 43.448 0.241 −41.556 1.00 37.92 A ATOM 47 CB THR A 79 43.983 1.662 −41.389 1.00 39.37 A ATOM 48 OG1 THR A 79 45.378 1.684 −41.710 1.00 42.97 A ATOM 49 CG2 THR A 79 43.770 2.143 −39.953 1.00 41.38 A ATOM 50 C THR A 79 43.700 −0.247 −42.965 1.00 37.15 A ATOM 51 O THR A 79 44.299 −1.298 −43.159 1.00 40.94 A ATOM 52 N CPR A 80 43.288 0.520 −43.969 1.00 34.90 A ATOM 53 CD CPR A 80 44.233 0.907 −45.032 1.00 33.68 A ATOM 54 CA CPR A 80 41.941 0.367 −44.515 1.00 31.75 A ATOM 55 CB CPR A 80 42.189 0.321 −46.016 1.00 32.26 A ATOM 56 CG CPR A 80 43.316 1.267 −46.177 1.00 34.32 A ATOM 57 C CPR A 80 41.207 −0.880 −44.023 1.00 29.73 A ATOM 58 O CPR A 80 41.726 −1.994 −44.105 1.00 28.01 A ATOM 59 N LEU A 81 40.000 −0.684 −43.504 1.00 26.29 A ATOM 60 CA LEU A 81 39.187 −1.805 −43.067 1.00 24.35 A ATOM 61 CB LEU A 81 38.007 −1.326 −42.218 1.00 20.43 A ATOM 62 CG LEU A 81 38.345 −0.696 −40.868 1.00 18.48 A ATOM 63 CD1 LEU A 81 37.074 −0.120 −40.242 1.00 10.91 A ATOM 64 CD2 LEU A 81 39.000 −1.749 −39.969 1.00 15.22 A ATOM 65 C LEU A 81 38.660 −2.430 −44.352 1.00 24.72 A ATOM 66 O LEU A 81 38.610 −1.772 −45.392 1.00 22.96 A ATOM 67 N LYS A 82 38.276 −3.698 −44.281 1.00 26.20 A ATOM 68 CA LYS A 82 37.738 −4.402 −45.441 1.00 26.69 A ATOM 69 CB LYS A 82 38.682 −5.540 −45.852 1.00 28.51 A ATOM 70 CG LYS A 82 38.188 −6.384 −47.022 1.00 34.36 A ATOM 71 CD LYS A 82 39.217 −7.445 −47.429 1.00 37.34 A ATOM 72 CE LYS A 82 38.722 −8.278 −48.609 1.00 39.22 A ATOM 73 NZ LYS A 82 39.762 −9.208 −49.129 1.00 41.01 A ATOM 74 C LYS A 82 36.366 −4.955 −45.059 1.00 25.07 A ATOM 75 O LYS A 82 36.169 −5.422 −43.940 1.00 25.23 A ATOM 76 N ILE A 83 35.417 −4.896 −45.986 1.00 22.76 A ATOM 77 CA ILE A 83 34.074 −5.387 −45.713 1.00 20.03 A ATOM 78 CB ILE A 83 33.061 −4.820 −46.717 1.00 17.56 A ATOM 79 CG2 ILE A 83 31.687 −5.395 −46.443 1.00 14.23 A ATOM 80 CG1 ILE A 83 33.050 −3.292 −46.642 1.00 14.83 A ATOM 81 CD1 ILE A 83 32.504 −2.738 −45.351 1.00 18.36 A ATOM 82 C ILE A 83 34.007 −6.905 −45.770 1.00 19.27 A ATOM 83 O ILE A 83 34.519 −7.520 −46.697 1.00 20.95 A ATOM 84 N VAL A 84 33.369 −7.498 −44.770 1.00 18.88 A ATOM 85 CA VAL A 84 33.209 −8.943 −44.689 1.00 18.55 A ATOM 86 CB VAL A 84 33.199 −9.409 −43.220 1.00 18.38 A ATOM 87 CG1 VAL A 84 32.826 −10.874 −43.136 1.00 17.47 A ATOM 88 CG2 VAL A 84 34.566 −9.166 −42.593 1.00 16.32 A ATOM 89 C VAL A 84 31.877 −9.299 −45.343 1.00 19.91 A ATOM 90 O VAL A 84 30.832 −8.759 −44.972 1.00 21.19 A ATOM 91 N GLU A 85 31.912 −10.210 −46.311 1.00 19.07 A ATOM 92 CA GLU A 85 30.700 −10.597 −47.022 1.00 18.15 A ATOM 93 CB GLU A 85 30.957 −10.620 −48.535 1.00 19.75 A ATOM 94 CG GLU A 85 31.242 −9.268 −49.179 1.00 20.83 A ATOM 95 CD GLU A 85 31.658 −9.413 −50.642 1.00 24.60 A ATOM 96 OE1 GLU A 85 31.043 −10.251 −51.350 1.00 24.61 A ATOM 97 OE2 GLU A 85 32.587 −8.691 −51.086 1.00 23.72 A ATOM 98 C GLU A 85 30.144 −11.948 −46.615 1.00 16.54 A ATOM 99 O GLU A 85 30.891 −12.871 −46.289 1.00 15.61 A ATOM 100 N TYR A 86 28.816 −12.040 −46.642 1.00 14.81 A ATOM 101 CA TYR A 86 28.086 −13.273 −46.342 1.00 13.38 A ATOM 102 CB TYR A 86 26.585 −13.045 −46.614 1.00 13.37 A ATOM 103 CG TYR A 86 25.740 −14.294 −46.671 1.00 11.64 A ATOM 104 CD1 TYR A 86 25.387 −14.988 −45.508 1.00 12.48 A ATOM 105 CE1 TYR A 86 24.653 −16.180 −45.576 1.00 9.76 A ATOM 106 CD2 TYR A 86 25.330 −14.815 −47.900 1.00 10.58 A ATOM 107 CE2 TYR A 86 24.602 −15.993 −47.979 1.00 7.91 A ATOM 108 CZ TYR A 86 24.271 −16.676 −46.821 1.00 9.19 A ATOM 109 OH TYR A 86 23.624 −17.891 −46.923 1.00 9.80 A ATOM 110 C TYR A 86 28.660 −14.288 −47.326 1.00 11.79 A ATOM 111 O TYR A 86 29.028 −13.922 −48.443 1.00 9.00 A ATOM 112 N PRO A 87 28.737 −15.571 −46.940 1.00 13.07 A ATOM 113 CD PRO A 87 29.187 −16.597 −47.904 1.00 12.32 A ATOM 114 CA PRO A 87 28.335 −16.193 −45.672 1.00 14.67 A ATOM 115 CB PRO A 87 27.876 −17.563 −46.122 1.00 13.93 A ATOM 116 CG PRO A 87 28.972 −17.908 −47.144 1.00 13.84 A ATOM 117 C PRO A 87 29.449 −16.289 −44.612 1.00 16.37 A ATOM 118 O PRO A 87 29.415 −17.176 −43.751 1.00 16.16 A ATOM 119 N ASP A 88 30.433 −15.396 −44.676 1.00 14.88 A ATOM 120 CA ASP A 88 31.529 −15.427 −43.708 1.00 16.94 A ATOM 121 CB ASP A 88 32.374 −14.155 −43.811 1.00 17.27 A ATOM 122 CG ASP A 88 33.647 −14.237 −42.991 1.00 20.01 A ATOM 123 OD1 ASP A 88 33.564 −14.530 −41.779 1.00 22.56 A ATOM 124 OD2 ASP A 88 34.734 −14.005 −43.559 1.00 22.48 A ATOM 125 C ASP A 88 30.964 −15.563 −42.286 1.00 17.02 A ATOM 126 O ASP A 88 30.111 −14.771 −41.864 1.00 14.24 A ATOM 127 N PRO A 89 31.454 −16.562 −41.528 1.00 17.30 A ATOM 128 CD PRO A 89 32.572 −17.414 −41.972 1.00 17.85 A ATOM 129 CA PRO A 89 31.063 −16.896 −40.148 1.00 16.77 A ATOM 130 CB PRO A 89 32.039 −18.014 −39.769 1.00 17.99 A ATOM 131 CG PRO A 89 32.412 −18.623 −41.091 1.00 19.05 A ATOM 132 C PRO A 89 31.102 −15.742 −39.141 1.00 17.05 A ATOM 133 O PRO A 89 30.343 −15.737 −38.167 1.00 14.98 A ATOM 134 N ILE A 90 31.997 −14.781 −39.371 1.00 16.08 A ATOM 135 CA ILE A 90 32.138 −13.624 −38.489 1.00 15.58 A ATOM 136 CB ILE A 90 33.228 −12.657 −39.019 1.00 14.80 A ATOM 137 CG2 ILE A 90 33.261 −11.394 −38.178 1.00 12.19 A ATOM 138 CG1 ILE A 90 34.596 −13.344 −38.983 1.00 15.77 A ATOM 139 CD1 ILE A 90 35.729 −12.544 −39.637 1.00 14.96 A ATOM 140 C ILE A 90 30.823 −12.853 −38.332 1.00 15.25 A ATOM 141 O ILE A 90 30.595 −12.190 −37.318 1.00 13.85 A ATOM 142 N LEU A 91 29.951 −12.960 −39.329 1.00 13.85 A ATOM 143 CA LEU A 91 28.679 −12.262 −39.295 1.00 12.86 A ATOM 144 CB LEU A 91 28.124 −12.129 −40.709 1.00 8.77 A ATOM 145 CG LEU A 91 29.118 −11.425 −41.639 1.00 8.91 A ATOM 146 CD1 LEU A 91 28.533 −11.337 −43.034 1.00 9.63 A ATOM 147 CD2 LEU A 91 29.460 −10.035 −41.096 1.00 7.28 A ATOM 148 C LEU A 91 27.666 −12.934 −38.383 1.00 14.00 A ATOM 149 O LEU A 91 26.585 −12.392 −38.147 1.00 15.75 A ATOM 150 N ARG A 92 28.024 −14.102 −37.856 1.00 14.41 A ATOM 151 CA ARG A 92 27.142 −14.841 −36.946 1.00 16.37 A ATOM 152 CB ARG A 92 26.771 −16.202 −37.541 1.00 17.16 A ATOM 153 CG ARG A 92 26.132 −16.163 −38.904 1.00 17.07 A ATOM 154 CD ARG A 92 24.720 −15.650 −38.825 1.00 17.49 A ATOM 155 NE ARG A 92 23.973 −15.900 −40.058 1.00 16.77 A ATOM 156 CZ ARG A 92 22.704 −15.549 −40.237 1.00 15.33 A ATOM 157 NH1 ARG A 92 22.042 −14.928 −39.263 1.00 15.95 A ATOM 158 NH2 ARG A 92 22.093 −15.828 −41.378 1.00 15.85 A ATOM 159 C ARG A 92 27.832 −15.099 −35.609 1.00 16.73 A ATOM 160 O ARG A 92 27.185 −15.475 −34.636 1.00 16.22 A ATOM 161 N ALA A 93 29.142 −14.874 −35.582 1.00 18.23 A ATOM 162 CA ALA A 93 30.006 −15.132 −34.425 1.00 22.48 A ATOM 163 CB ALA A 93 31.457 −14.786 −34.797 1.00 23.31 A ATOM 164 C ALA A 93 29.726 −14.602 −33.015 1.00 24.67 A ATOM 165 O ALA A 93 30.506 −14.902 −32.106 1.00 28.53 A ATOM 166 N LYS A 94 28.665 −13.833 −32.799 1.00 24.09 A ATOM 167 CA LYS A 94 28.384 −13.346 −31.439 1.00 24.96 A ATOM 168 CB LYS A 94 28.436 −14.500 −30.437 1.00 25.30 A ATOM 169 CG LYS A 94 28.341 −14.049 −29.000 1.00 29.01 A ATOM 170 CD LYS A 94 29.295 −14.836 −28.131 1.00 32.16 A ATOM 171 CE LYS A 94 29.502 −14.124 −26.805 1.00 33.93 A ATOM 172 NZ LYS A 94 29.929 −12.709 −27.033 1.00 34.32 A ATOM 173 C LYS A 94 29.371 −12.256 −31.016 1.00 22.46 A ATOM 174 O LYS A 94 30.581 −12.475 −30.959 1.00 21.86 A ATOM 175 N ASN A 95 28.832 −11.093 −30.673 1.00 21.41 A ATOM 176 CA ASN A 95 29.657 −9.946 −30.341 1.00 22.01 A ATOM 177 CB ASN A 95 29.187 −8.774 −31.208 1.00 20.42 A ATOM 178 CG ASN A 95 28.983 −9.187 −32.651 1.00 19.92 A ATOM 179 OD1 ASN A 95 27.859 −9.463 −33.085 1.00 18.30 A ATOM 180 ND2 ASN A 95 30.081 −9.268 −33.397 1.00 20.07 A ATOM 181 C ASN A 95 29.774 −9.517 −28.884 1.00 21.39 A ATOM 182 O ASN A 95 28.777 −9.287 −28.199 1.00 20.41 A ATOM 183 N LYS A 96 31.019 −9.395 −28.434 1.00 23.00 A ATOM 184 CA LYS A 96 31.334 −8.989 −27.071 1.00 23.73 A ATOM 185 CB LYS A 96 32.779 −9.351 −26.732 1.00 25.32 A ATOM 186 CG LYS A 96 33.051 −10.845 −26.646 1.00 26.59 A ATOM 187 CD LYS A 96 34.537 −11.110 −26.428 1.00 30.79 A ATOM 188 CE LYS A 96 34.831 −12.599 −26.255 1.00 32.28 A ATOM 189 NZ LYS A 96 36.296 −12.888 −26.289 1.00 32.84 A ATOM 190 C LYS A 96 31.135 −7.492 −26.874 1.00 25.90 A ATOM 191 O LYS A 96 31.421 −6.686 −27.769 1.00 25.26 A ATOM 192 N ARG A 97 30.642 −7.134 −25.692 1.00 26.74 A ATOM 193 CA ARG A 97 30.402 −5.743 −25.336 1.00 27.69 A ATOM 194 CB ARG A 97 29.702 −5.662 −23.979 1.00 28.92 A ATOM 195 CG ARG A 97 28.317 −6.287 −23.952 1.00 33.87 A ATOM 196 CD ARG A 97 27.813 −6.493 −22.525 1.00 37.61 A ATOM 197 NE ARG A 97 28.062 −5.314 −21.706 1.00 39.27 A ATOM 198 CZ ARG A 97 29.170 −5.119 −20.999 1.00 40.73 A ATOM 199 NH1 ARG A 97 30.132 −6.035 −20.995 1.00 41.21 A ATOM 200 NH2 ARG A 97 29.334 −3.987 −20.330 1.00 40.81 A ATOM 201 C ARG A 97 31.730 −5.009 −25.262 1.00 27.45 A ATOM 202 O ARG A 97 32.773 −5.619 −25.014 1.00 27.82 A ATOM 203 N ILE A 98 31.689 −3.702 −25.487 1.00 25.11 A ATOM 204 CA ILE A 98 32.889 −2.888 −25.426 1.00 24.66 A ATOM 205 CB ILE A 98 32.866 −1.803 −26.529 1.00 24.88 A ATOM 206 CG2 ILE A 98 33.965 −0.767 −26.301 1.00 20.36 A ATOM 207 CG1 ILE A 98 33.044 −2.485 −27.891 1.00 24.66 A ATOM 208 CD1 ILE A 98 33.092 −1.538 −29.061 1.00 28.24 A ATOM 209 C ILE A 98 32.997 −2.267 −24.035 1.00 24.19 A ATOM 210 O ILE A 98 32.093 −1.571 −23.581 1.00 24.25 A ATOM 211 N ASP A 99 34.104 −2.549 −23.359 1.00 23.56 A ATOM 212 CA ASP A 99 34.339 −2.053 −22.008 1.00 23.39 A ATOM 213 CB ASP A 99 34.250 −3.214 −21.018 1.00 23.94 A ATOM 214 CG ASP A 99 35.163 −4.366 −21.394 1.00 24.05 A ATOM 215 OD1 ASP A 99 35.055 −5.439 −20.766 1.00 24.51 A ATOM 216 OD2 ASP A 99 35.991 −4.196 −22.318 1.00 23.12 A ATOM 217 C ASP A 99 35.699 −1.370 −21.880 1.00 23.34 A ATOM 218 O ASP A 99 36.285 −1.317 −20.800 1.00 21.90 A ATOM 219 N ILE A 100 36.204 −0.875 −23.002 1.00 22.91 A ATOM 220 CA ILE A 100 37.469 −0.161 −23.033 1.00 22.92 A ATOM 221 CB ILE A 100 38.647 −1.068 −23.461 1.00 21.59 A ATOM 222 CG2 ILE A 100 39.872 −0.209 −23.780 1.00 21.34 A ATOM 223 CG1 ILE A 100 38.960 −2.072 −22.342 1.00 20.46 A ATOM 224 CD1 ILE A 100 40.247 −2.845 −22.530 1.00 16.61 A ATOM 225 C ILE A 100 37.292 0.975 −24.026 1.00 23.77 A ATOM 226 O ILE A 100 37.268 0.767 −25.243 1.00 22.69 A ATOM 227 N PHE A 101 37.145 2.179 −23.489 1.00 23.83 A ATOM 228 CA PHE A 101 36.934 3.360 −24.308 1.00 24.41 A ATOM 229 CB PHE A 101 35.788 4.175 −23.705 1.00 23.98 A ATOM 230 CG PHE A 101 34.559 3.343 −23.419 1.00 24.14 A ATOM 231 CD1 PHE A 101 34.480 2.567 −22.261 1.00 25.77 A ATOM 232 CD2 PHE A 101 33.517 3.274 −24.339 1.00 23.97 A ATOM 233 CE1 PHE A 101 33.379 1.729 −22.025 1.00 26.25 A ATOM 234 CE2 PHE A 101 32.413 2.444 −24.115 1.00 24.68 A ATOM 235 CZ PHE A 101 32.344 1.669 −22.958 1.00 24.94 A ATOM 236 C PHE A 101 38.227 4.152 −24.398 1.00 24.03 A ATOM 237 O PHE A 101 38.514 5.009 −23.565 1.00 24.43 A ATOM 238 N ASP A 102 39.002 3.840 −25.435 1.00 23.26 A ATOM 239 CA ASP A 102 40.301 4.458 −25.658 1.00 22.30 A ATOM 240 CB ASP A 102 41.408 3.437 −25.360 1.00 22.09 A ATOM 241 CG ASP A 102 41.328 2.199 −26.256 1.00 20.92 A ATOM 242 OD1 ASP A 102 40.445 2.141 −27.143 1.00 18.72 A ATOM 243 OD2 ASP A 102 42.158 1.279 −26.072 1.00 20.13 A ATOM 244 C ASP A 102 40.495 4.990 −27.066 1.00 21.70 A ATOM 245 O ASP A 102 39.567 5.025 −27.868 1.00 22.38 A ATOM 246 N GLU A 103 41.728 5.398 −27.349 1.00 22.47 A ATOM 247 CA GLU A 103 42.108 5.927 −28.653 1.00 21.29 A ATOM 248 CB GLU A 103 43.610 6.188 −28.705 1.00 19.68 A ATOM 249 CG GLU A 103 43.965 7.635 −28.642 1.00 21.47 A ATOM 250 CD GLU A 103 43.305 8.423 −29.741 1.00 21.50 A ATOM 251 OE1 GLU A 103 42.668 9.445 −29.427 1.00 20.68 A ATOM 252 OE2 GLU A 103 43.427 8.020 −30.914 1.00 22.92 A ATOM 253 C GLU A 103 41.764 4.954 −29.754 1.00 20.91 A ATOM 254 O GLU A 103 41.172 5.331 −30.767 1.00 19.57 A ATOM 255 N ASN A 104 42.172 3.705 −29.550 1.00 21.14 A ATOM 256 CA ASN A 104 41.937 2.639 −30.507 1.00 22.17 A ATOM 257 CB ASN A 104 42.341 1.299 −29.897 1.00 26.29 A ATOM 258 CG ASN A 104 43.312 0.541 −30.766 1.00 29.79 A ATOM 259 OD1 ASN A 104 43.027 0.261 −31.930 1.00 33.45 A ATOM 260 ND2 ASN A 104 44.473 0.204 −30.208 1.00 30.61 A ATOM 261 C ASN A 104 40.473 2.593 −30.920 1.00 22.03 A ATOM 262 O ASN A 104 40.160 2.479 −32.108 1.00 21.05 A ATOM 263 N LEU A 105 39.581 2.684 −29.934 1.00 19.85 A ATOM 264 CA LEU A 105 38.150 2.657 −30.199 1.00 19.86 A ATOM 265 CB LEU A 105 37.358 2.735 −28.886 1.00 21.38 A ATOM 266 CG LEU A 105 35.919 2.188 −28.821 1.00 21.48 A ATOM 267 CD1 LEU A 105 35.056 3.165 −28.032 1.00 21.52 A ATOM 268 CD2 LEU A 105 35.341 1.980 −30.207 1.00 21.83 A ATOM 269 C LEU A 105 37.771 3.830 −31.102 1.00 19.11 A ATOM 270 O LEU A 105 36.987 3.668 −32.036 1.00 19.29 A ATOM 271 N LYS A 106 38.328 5.008 −30.820 1.00 17.86 A ATOM 272 CA LYS A 106 38.051 6.194 −31.627 1.00 18.70 A ATOM 273 CB LYS A 106 38.639 7.449 −30.974 1.00 18.90 A ATOM 274 CG LYS A 106 38.329 8.737 −31.744 1.00 21.08 A ATOM 275 CD LYS A 106 38.916 9.962 −31.051 1.00 20.57 A ATOM 276 CE LYS A 106 40.425 10.037 −31.200 1.00 19.98 A ATOM 277 NZ LYS A 106 41.013 11.166 −30.404 1.00 18.10 A ATOM 278 C LYS A 106 38.597 6.061 −33.058 1.00 18.80 A ATOM 279 O LYS A 106 37.914 6.413 −34.023 1.00 18.37 A ATOM 280 N ASN A 107 39.822 5.556 −33.190 1.00 17.20 A ATOM 281 CA ASN A 107 40.431 5.370 −34.506 1.00 18.47 A ATOM 282 CB ASN A 107 41.857 4.814 −34.363 1.00 21.05 A ATOM 283 CG ASN A 107 42.777 5.725 −33.544 1.00 24.77 A ATOM 284 OD1 ASN A 107 43.803 5.275 −33.021 1.00 26.42 A ATOM 285 ND2 ASN A 107 42.423 7.005 −33.441 1.00 23.25 A ATOM 286 C ASN A 107 39.587 4.394 −35.332 1.00 17.56 A ATOM 287 O ASN A 107 39.453 4.543 −36.545 1.00 17.37 A ATOM 288 N LEU A 108 39.008 3.401 −34.659 1.00 18.87 A ATOM 289 CA LEU A 108 38.182 2.393 −35.315 1.00 18.66 A ATOM 290 CB LEU A 108 37.754 1.318 −34.310 1.00 17.82 A ATOM 291 CG LEU A 108 37.452 −0.094 −34.834 1.00 18.20 A ATOM 292 CD1 LEU A 108 36.611 −0.846 −33.809 1.00 14.71 A ATOM 293 CD2 LEU A 108 36.712 −0.033 −36.137 1.00 16.41 A ATOM 294 C LEU A 108 36.938 3.025 −35.936 1.00 19.55 A ATOM 295 O LEU A 108 36.669 2.851 −37.127 1.00 20.36 A ATOM 296 N VAL A 109 36.183 3.752 −35.117 1.00 19.78 A ATOM 297 CA VAL A 109 34.961 4.412 −35.567 1.00 20.39 A ATOM 298 CB VAL A 109 34.391 5.350 −34.460 1.00 20.97 A ATOM 299 CG1 VAL A 109 33.245 6.201 −35.014 1.00 18.35 A ATOM 300 CG2 VAL A 109 33.908 4.514 −33.282 1.00 18.10 A ATOM 301 C VAL A 109 35.207 5.218 −36.841 1.00 21.06 A ATOM 302 O VAL A 109 34.448 5.104 −37.815 1.00 20.21 A ATOM 303 N ASP A 110 36.268 6.021 −36.833 1.00 19.90 A ATOM 304 CA ASP A 110 36.609 6.834 −37.993 1.00 19.28 A ATOM 305 CB ASP A 110 37.787 7.760 −37.665 1.00 21.34 A ATOM 306 CG ASP A 110 38.385 8.412 −38.904 1.00 23.52 A ATOM 307 OD1 ASP A 110 39.280 7.805 −39.525 1.00 23.06 A ATOM 308 OD2 ASP A 110 37.950 9.526 −39.264 1.00 25.77 A ATOM 309 C ASP A 110 36.954 5.948 −39.187 1.00 18.12 A ATOM 310 O ASP A 110 36.606 6.260 −40.326 1.00 16.99 A ATOM 311 N ALA A 111 37.640 4.842 −38.928 1.00 17.77 A ATOM 312 CA ALA A 111 38.007 3.934 −40.014 1.00 18.12 A ATOM 313 CB ALA A 111 38.991 2.879 −39.517 1.00 17.41 A ATOM 314 C ALA A 111 36.747 3.265 −40.559 1.00 18.06 A ATOM 315 O ALA A 111 36.688 2.909 −41.735 1.00 17.71 A ATOM 316 N MET A 112 35.741 3.093 −39.700 1.00 16.57 A ATOM 317 CA MET A 112 34.493 2.476 −40.131 1.00 16.68 A ATOM 318 CB MET A 112 33.625 2.094 −38.932 1.00 16.96 A ATOM 319 CG MET A 112 34.095 0.844 −38.224 1.00 15.01 A ATOM 320 SD MET A 112 33.117 0.488 −36.768 1.00 19.27 A ATOM 321 CE MET A 112 31.718 −0.406 −37.514 1.00 17.01 A ATOM 322 C MET A 112 33.729 3.421 −41.036 1.00 16.16 A ATOM 323 O MET A 112 33.206 3.009 −42.072 1.00 16.11 A ATOM 324 N PHE A 113 33.661 4.688 −40.643 1.00 16.28 A ATOM 325 CA PHE A 113 32.965 5.674 −41.458 1.00 18.18 A ATOM 326 CB PHE A 113 32.955 7.054 −40.770 1.00 16.66 A ATOM 327 CG PHE A 113 31.803 7.259 −39.806 1.00 14.71 A ATOM 328 CD1 PHE A 113 30.482 7.154 −40.239 1.00 14.21 A ATOM 329 CD2 PHE A 113 32.041 7.552 −38.457 1.00 15.65 A ATOM 330 CE1 PHE A 113 29.406 7.334 −39.341 1.00 12.91 A ATOM 331 CE2 PHE A 113 30.979 7.735 −37.554 1.00 13.65 A ATOM 332 CZ PHE A 113 29.658 7.624 −38.001 1.00 13.65 A ATOM 333 C PHE A 113 33.674 5.763 −42.813 1.00 19.19 A ATOM 334 O PHE A 113 33.036 5.966 −43.848 1.00 20.51 A ATOM 335 N ASP A 114 34.993 5.593 −42.809 1.00 19.06 A ATOM 336 CA ASP A 114 35.752 5.671 −44.050 1.00 19.17 A ATOM 337 CB ASP A 114 37.258 5.516 −43.800 1.00 19.27 A ATOM 338 CG ASP A 114 37.847 6.649 −42.972 1.00 18.16 A ATOM 339 OD1 ASP A 114 37.388 7.798 −43.112 1.00 18.34 A ATOM 340 OD2 ASP A 114 38.792 6.383 −42.194 1.00 16.95 A ATOM 341 C ASP A 114 35.328 4.601 −45.047 1.00 20.74 A ATOM 342 O ASP A 114 34.948 4.905 −46.178 1.00 22.18 A ATOM 343 N VAL A 115 35.402 3.343 −44.635 1.00 19.76 A ATOM 344 CA VAL A 115 35.051 2.271 −45.541 1.00 20.05 A ATOM 345 CB VAL A 115 35.421 0.882 −44.952 1.00 18.79 A ATOM 346 CG1 VAL A 115 34.508 0.535 −43.781 1.00 19.87 A ATOM 347 CG2 VAL A 115 35.348 −0.179 −46.047 1.00 18.66 A ATOM 348 C VAL A 115 33.570 2.319 −45.888 1.00 20.92 A ATOM 349 O VAL A 115 33.172 1.900 −46.976 1.00 21.72 A ATOM 350 N MET A 116 32.756 2.843 −44.975 1.00 20.52 A ATOM 351 CA MET A 116 31.324 2.928 −45.225 1.00 20.64 A ATOM 352 CB MET A 116 30.574 3.419 −43.975 1.00 21.83 A ATOM 353 CG MET A 116 29.047 3.419 −44.133 1.00 21.70 A ATOM 354 SD MET A 116 28.146 4.174 −42.758 1.00 25.32 A ATOM 355 CE MET A 116 28.020 5.885 −43.298 1.00 22.79 A ATOM 356 C MET A 116 31.107 3.896 −46.387 1.00 21.10 A ATOM 357 O MET A 116 30.475 3.544 −47.389 1.00 18.06 A ATOM 358 N TYR A 117 31.652 5.106 −46.247 1.00 21.03 A ATOM 359 CA TYR A 117 31.537 6.135 −47.275 1.00 20.92 A ATOM 360 CB TYR A 117 32.175 7.448 −46.809 1.00 20.51 A ATOM 361 CG TYR A 117 31.419 8.154 −45.709 1.00 18.43 A ATOM 362 CD1 TYR A 117 30.033 8.240 −45.744 1.00 17.94 A ATOM 363 CE1 TYR A 117 29.328 8.917 −44.754 1.00 18.18 A ATOM 364 CD2 TYR A 117 32.089 8.765 −44.652 1.00 17.61 A ATOM 365 CE2 TYR A 117 31.391 9.450 −43.655 1.00 17.47 A ATOM 366 CZ TYR A 117 30.011 9.518 −43.719 1.00 16.23 A ATOM 367 OH TYR A 117 29.301 10.186 −42.759 1.00 18.52 A ATOM 368 C TYR A 117 32.212 5.700 −48.563 1.00 22.73 A ATOM 369 O TYR A 117 31.717 5.976 −49.653 1.00 22.10 A ATOM 370 N LYS A 118 33.356 5.034 −48.434 1.00 24.25 A ATOM 371 CA LYS A 118 34.091 4.576 −49.602 1.00 25.84 A ATOM 372 CB LYS A 118 35.328 3.776 −49.188 1.00 26.26 A ATOM 373 CG LYS A 118 36.230 3.407 −50.364 1.00 30.30 A ATOM 374 CD LYS A 118 37.218 2.273 −50.035 1.00 31.07 A ATOM 375 CE LYS A 118 36.496 0.934 −49.841 1.00 32.32 A ATOM 376 NZ LYS A 118 37.410 −0.253 −49.726 1.00 29.48 A ATOM 377 C LYS A 118 33.189 3.687 −50.446 1.00 27.75 A ATOM 378 O LYS A 118 33.102 3.836 −51.667 1.00 27.33 A ATOM 379 N THR A 119 32.510 2.765 −49.774 1.00 28.14 A ATOM 380 CA THR A 119 31.637 1.814 −50.438 1.00 28.42 A ATOM 381 CB THR A 119 31.617 0.480 −49.649 1.00 28.33 A ATOM 382 OG1 THR A 119 31.330 0.739 −48.269 1.00 29.06 A ATOM 383 CG2 THR A 119 32.975 −0.211 −49.738 1.00 27.56 A ATOM 384 C THR A 119 30.223 2.354 −50.631 1.00 29.80 A ATOM 385 O THR A 119 29.297 1.607 −50.955 1.00 28.97 A ATOM 386 N ASP A 120 30.078 3.665 −50.454 1.00 31.38 A ATOM 387 CA ASP A 120 28.790 4.333 −50.605 1.00 32.18 A ATOM 388 CB ASP A 120 28.401 4.406 −52.092 1.00 34.50 A ATOM 389 CG ASP A 120 29.104 5.544 −52.828 1.00 38.27 A ATOM 390 OD1 ASP A 120 28.855 6.724 −52.478 1.00 40.42 A ATOM 391 OD2 ASP A 120 29.905 5.266 −53.752 1.00 38.92 A ATOM 392 C ASP A 120 27.724 3.599 −49.800 1.00 30.66 A ATOM 393 O ASP A 120 26.683 3.199 −50.323 1.00 31.17 A ATOM 394 N GLY A 121 28.012 3.415 −48.517 1.00 28.44 A ATOM 395 CA GLY A 121 27.087 2.734 −47.634 1.00 26.11 A ATOM 396 C GLY A 121 26.363 3.735 −46.755 1.00 25.00 A ATOM 397 O GLY A 121 26.607 4.944 −46.837 1.00 22.88 A ATOM 398 N ILE A 122 25.484 3.240 −45.894 1.00 23.50 A ATOM 399 CA ILE A 122 24.730 4.131 −45.032 1.00 23.79 A ATOM 400 CB ILE A 122 23.255 4.131 −45.452 1.00 24.10 A ATOM 401 CG2 ILE A 122 22.460 3.154 −44.612 1.00 23.83 A ATOM 402 CG1 ILE A 122 22.721 5.555 −45.390 1.00 23.51 A ATOM 403 CD1 ILE A 122 23.404 6.457 −46.381 1.00 22.10 A ATOM 404 C ILE A 122 24.852 3.766 −43.568 1.00 22.35 A ATOM 405 O ILE A 122 24.598 4.585 −42.685 1.00 21.65 A ATOM 406 N GLY A 123 25.240 2.521 −43.329 1.00 21.64 A ATOM 407 CA GLY A 123 25.405 2.018 −41.980 1.00 20.23 A ATOM 408 C GLY A 123 26.421 0.892 −41.999 1.00 20.31 A ATOM 409 O GLY A 123 26.645 0.250 −43.032 1.00 21.53 A ATOM 410 N LEU A 124 27.051 0.647 −40.860 1.00 19.19 A ATOM 411 CA LEU A 124 28.049 −0.405 −40.784 1.00 18.26 A ATOM 412 CB LEU A 124 29.366 0.095 −41.390 1.00 16.37 A ATOM 413 CG LEU A 124 30.540 −0.878 −41.504 1.00 18.75 A ATOM 414 CD1 LEU A 124 30.236 −1.928 −42.573 1.00 20.38 A ATOM 415 CD2 LEU A 124 31.803 −0.101 −41.868 1.00 17.41 A ATOM 416 C LEU A 124 28.264 −0.824 −39.336 1.00 17.38 A ATOM 417 O LEU A 124 28.340 0.014 −38.440 1.00 17.30 A ATOM 418 N SER A 125 28.352 −2.128 −39.113 1.00 16.59 A ATOM 419 CA SER A 125 28.578 −2.656 −37.782 1.00 15.38 A ATOM 420 CB SER A 125 27.498 −3.672 −37.429 1.00 15.89 A ATOM 421 OG SER A 125 27.537 −4.772 −38.323 1.00 20.69 A ATOM 422 C SER A 125 29.949 −3.324 −37.790 1.00 14.95 A ATOM 423 O SER A 125 30.388 −3.824 −38.819 1.00 13.32 A ATOM 424 N ALA A 126 30.616 −3.319 −36.641 1.00 13.72 A ATOM 425 CA ALA A 126 31.942 −3.903 −36.498 1.00 14.24 A ATOM 426 CB ALA A 126 32.362 −3.878 −35.034 1.00 13.11 A ATOM 427 C ALA A 126 32.089 −5.318 −37.060 1.00 14.55 A ATOM 428 O ALA A 126 33.113 −5.640 −37.663 1.00 16.65 A ATOM 429 N PRO A 127 31.083 −6.188 −36.859 1.00 15.05 A ATOM 430 CD PRO A 127 29.881 −6.062 −36.012 1.00 13.21 A ATOM 431 CA PRO A 127 31.205 −7.549 −37.395 1.00 14.59 A ATOM 432 CB PRO A 127 29.837 −8.155 −37.104 1.00 15.34 A ATOM 433 CG PRO A 127 29.489 −7.513 −35.782 1.00 14.66 A ATOM 434 C PRO A 127 31.522 −7.518 −38.885 1.00 15.75 A ATOM 435 O PRO A 127 32.242 −8.382 −39.400 1.00 12.00 A ATOM 436 N GLN A 128 30.993 −6.498 −39.559 1.00 15.65 A ATOM 437 CA GLN A 128 31.191 −6.323 −40.993 1.00 17.40 A ATOM 438 CB GLN A 128 30.180 −5.316 −41.542 1.00 16.39 A ATOM 439 CG GLN A 128 28.812 −5.917 −41.778 1.00 18.40 A ATOM 440 CD GLN A 128 27.801 −4.891 −42.228 1.00 20.84 A ATOM 441 OE1 GLN A 128 27.428 −4.002 −41.458 1.00 22.13 A ATOM 442 NE2 GLN A 128 27.350 −4.999 −43.482 1.00 18.66 A ATOM 443 C GLN A 128 32.603 −5.912 −41.396 1.00 19.05 A ATOM 444 O GLN A 128 32.919 −5.860 −42.584 1.00 20.10 A ATOM 445 N VAL A 129 33.448 −5.608 −40.418 1.00 19.63 A ATOM 446 CA VAL A 129 34.828 −5.241 −40.712 1.00 20.04 A ATOM 447 CB VAL A 129 35.152 −3.775 −40.284 1.00 20.18 A ATOM 448 CG1 VAL A 129 34.404 −2.805 −41.161 1.00 18.05 A ATOM 449 CG2 VAL A 129 34.780 −3.546 −38.829 1.00 19.45 A ATOM 450 C VAL A 129 35.773 −6.216 −40.002 1.00 21.14 A ATOM 451 O VAL A 129 36.959 −5.944 −39.844 1.00 21.90 A ATOM 452 N GLY A 130 35.228 −7.348 −39.561 1.00 22.19 A ATOM 453 CA GLY A 130 36.035 −8.368 −38.907 1.00 20.21 A ATOM 454 C GLY A 130 36.113 −8.351 −37.390 1.00 19.73 A ATOM 455 O GLY A 130 36.776 −9.201 −36.790 1.00 18.88 A ATOM 456 N LEU A 131 35.445 −7.396 −36.758 1.00 17.97 A ATOM 457 CA LEU A 131 35.488 −7.307 −35.305 1.00 16.71 A ATOM 458 CB LEU A 131 35.860 −5.890 −34.878 1.00 17.61 A ATOM 459 CG LEU A 131 37.335 −5.519 −35.060 1.00 19.78 A ATOM 460 CD1 LEU A 131 37.765 −5.704 −36.509 1.00 21.35 A ATOM 461 CD2 LEU A 131 37.539 −4.091 −34.629 1.00 17.99 A ATOM 462 C LEU A 131 34.175 −7.717 −34.662 1.00 16.20 A ATOM 463 O LEU A 131 33.110 −7.171 −34.979 1.00 16.20 A ATOM 464 N ASN A 132 34.249 −8.687 −33.758 1.00 15.11 A ATOM 465 CA ASN A 132 33.049 −9.158 −33.092 1.00 14.07 A ATOM 466 CB ASN A 132 33.109 −10.675 −32.904 1.00 14.53 A ATOM 467 CG ASN A 132 32.921 −11.420 −34.221 1.00 15.08 A ATOM 468 OD1 ASN A 132 33.885 −11.786 −34.882 1.00 17.92 A ATOM 469 ND2 ASN A 132 31.673 −11.611 −34.617 1.00 13.68 A ATOM 470 C ASN A 132 32.768 −8.444 −31.780 1.00 13.50 A ATOM 471 O ASN A 132 32.749 −9.050 −30.708 1.00 13.65 A ATOM 472 N VAL A 133 32.549 −7.138 −31.890 1.00 12.59 A ATOM 473 CA VAL A 133 32.242 −6.307 −30.741 1.00 13.93 A ATOM 474 CB VAL A 133 33.409 −5.347 −30.416 1.00 10.85 A ATOM 475 CG1 VAL A 133 34.607 −6.149 −29.931 1.00 10.23 A ATOM 476 CG2 VAL A 133 33.784 −4.544 −31.638 1.00 10.25 A ATOM 477 C VAL A 133 30.971 −5.513 −31.018 1.00 13.57 A ATOM 478 O VAL A 133 30.563 −5.364 −32.162 1.00 13.60 A ATOM 479 N GLN A 134 30.353 −5.002 −29.963 1.00 15.90 A ATOM 480 CA GLN A 134 29.111 −4.246 −30.100 1.00 17.13 A ATOM 481 CB GLN A 134 28.276 −4.439 −28.831 1.00 15.99 A ATOM 482 CG GLN A 134 27.851 −5.906 −28.679 1.00 17.43 A ATOM 483 CD GLN A 134 27.161 −6.217 −27.368 1.00 19.77 A ATOM 484 OE1 GLN A 134 26.439 −5.386 −26.822 1.00 23.84 A ATOM 485 NE2 GLN A 134 27.359 −7.433 −26.866 1.00 18.29 A ATOM 486 C GLN A 134 29.324 −2.771 −30.423 1.00 16.76 A ATOM 487 O GLN A 134 29.182 −1.900 −29.566 1.00 16.52 A ATOM 488 N LEU A 135 29.672 −2.515 −31.682 1.00 15.24 A ATOM 489 CA LEU A 135 29.928 −1.162 −32.172 1.00 15.82 A ATOM 490 CB LEU A 135 31.436 −0.933 −32.344 1.00 14.00 A ATOM 491 CG LEU A 135 31.828 0.460 −32.840 1.00 15.40 A ATOM 492 CD1 LEU A 135 31.450 1.490 −31.775 1.00 14.23 A ATOM 493 CD2 LEU A 135 33.322 0.508 −33.163 1.00 12.52 A ATOM 494 C LEU A 135 29.218 −0.931 −33.502 1.00 14.99 A ATOM 495 O LEU A 135 29.251 −1.773 −34.400 1.00 15.49 A ATOM 496 N MET A 136 28.608 0.235 −33.638 1.00 16.04 A ATOM 497 CA MET A 136 27.859 0.561 −34.841 1.00 18.35 A ATOM 498 CB MET A 136 26.396 0.180 −34.588 1.00 19.43 A ATOM 499 CG MET A 136 25.375 0.880 −35.438 1.00 23.19 A ATOM 500 SD MET A 136 23.777 0.872 −34.619 1.00 26.18 A ATOM 501 CE MET A 136 23.640 −0.872 −34.190 1.00 22.49 A ATOM 502 C MET A 136 27.967 2.039 −35.255 1.00 19.14 A ATOM 503 O MET A 136 28.119 2.934 −34.408 1.00 18.03 A ATOM 504 N VAL A 137 27.904 2.284 −36.563 1.00 18.64 A ATOM 505 CA VAL A 137 27.941 3.643 −37.094 1.00 19.57 A ATOM 506 CB VAL A 137 29.354 4.075 −37.558 1.00 21.08 A ATOM 507 CG1 VAL A 137 30.374 3.826 −36.451 1.00 20.89 A ATOM 508 CG2 VAL A 137 29.723 3.356 −38.854 1.00 20.49 A ATOM 509 C VAL A 137 27.018 3.757 −38.301 1.00 20.02 A ATOM 510 O VAL A 137 26.667 2.754 −38.933 1.00 18.78 A ATOM 511 N PHE A 138 26.621 4.985 −38.614 1.00 20.79 A ATOM 512 CA PHE A 138 25.771 5.225 −39.762 1.00 22.08 A ATOM 513 CB PHE A 138 24.451 4.446 −39.629 1.00 23.84 A ATOM 514 CG PHE A 138 23.535 4.947 −38.549 1.00 22.93 A ATOM 515 CD1 PHE A 138 22.588 5.926 −38.822 1.00 25.45 A ATOM 516 CD2 PHE A 138 23.584 4.405 −37.268 1.00 25.82 A ATOM 517 CE1 PHE A 138 21.692 6.357 −37.832 1.00 24.76 A ATOM 518 CE2 PHE A 138 22.697 4.829 −36.271 1.00 25.19 A ATOM 519 CZ PHE A 138 21.748 5.807 −36.558 1.00 24.73 A ATOM 520 C PHE A 138 25.511 6.705 −39.982 1.00 23.31 A ATOM 521 O PHE A 138 25.671 7.530 −39.071 1.00 21.01 A ATOM 522 N ASN A 139 25.137 7.026 −41.216 1.00 24.83 A ATOM 523 CA ASN A 139 24.838 8.388 −41.622 1.00 26.78 A ATOM 524 CB ASN A 139 26.104 9.080 −42.113 1.00 28.84 A ATOM 525 CG ASN A 139 25.919 10.574 −42.268 1.00 31.35 A ATOM 526 OD1 ASN A 139 24.951 11.031 −42.876 1.00 29.99 A ATOM 527 ND2 ASN A 139 26.850 11.346 −41.717 1.00 31.87 A ATOM 528 C ASN A 139 23.826 8.305 −42.762 1.00 27.67 A ATOM 529 O ASN A 139 24.147 7.834 −43.850 1.00 26.38 A ATOM 530 N PRO A 140 22.587 8.762 −42.522 1.00 28.57 A ATOM 531 CD PRO A 140 22.108 9.409 −41.288 1.00 27.09 A ATOM 532 CA PRO A 140 21.525 8.733 −43.531 1.00 29.40 A ATOM 533 CB PRO A 140 20.451 9.626 −42.923 1.00 27.26 A ATOM 534 CG PRO A 140 20.606 9.366 −41.472 1.00 28.54 A ATOM 535 C PRO A 140 21.976 9.231 −44.892 1.00 29.84 A ATOM 536 O PRO A 140 21.655 8.635 −45.914 1.00 30.11 A ATOM 537 N ALA A 141 22.716 10.332 −44.897 1.00 31.08 A ATOM 538 CA ALA A 141 23.200 10.921 −46.138 1.00 33.10 A ATOM 539 CB ALA A 141 23.945 12.207 −45.838 1.00 32.04 A ATOM 540 C ALA A 141 24.095 9.969 −46.928 1.00 34.75 A ATOM 541 O ALA A 141 23.899 9.777 −48.129 1.00 34.87 A ATOM 542 N GLY A 142 25.079 9.380 −46.253 1.00 36.61 A ATOM 543 CA GLY A 142 25.989 8.461 −46.916 1.00 38.38 A ATOM 544 C GLY A 142 27.181 9.178 −47.519 1.00 39.97 A ATOM 545 O GLY A 142 28.022 8.559 −48.175 1.00 40.45 A ATOM 546 N GLU A 143 27.248 10.487 −47.293 1.00 41.61 A ATOM 547 CA GLU A 143 28.327 11.321 −47.808 1.00 43.02 A ATOM 548 CB GLU A 143 27.765 12.402 −48.737 1.00 44.16 A ATOM 549 CG GLU A 143 26.697 11.917 −49.707 1.00 47.41 A ATOM 550 CD GLU A 143 27.262 11.131 −50.874 1.00 49.37 A ATOM 551 OE1 GLU A 143 28.046 10.183 −50.645 1.00 50.56 A ATOM 552 OE2 GLU A 143 26.914 11.463 −52.027 1.00 51.60 A ATOM 553 C GLU A 143 29.014 12.000 −46.630 1.00 43.65 A ATOM 554 O GLU A 143 28.353 12.483 −45.710 1.00 42.94 A ATOM 555 N PRO A 144 30.351 12.046 −46.639 1.00 44.50 A ATOM 556 CD PRO A 144 31.298 11.494 −47.620 1.00 44.64 A ATOM 557 CA PRO A 144 31.062 12.690 −45.535 1.00 45.86 A ATOM 558 CB PRO A 144 32.525 12.567 −45.947 1.00 44.41 A ATOM 559 CG PRO A 144 32.539 11.336 −46.788 1.00 44.69 A ATOM 560 C PRO A 144 30.624 14.146 −45.431 1.00 47.73 A ATOM 561 O PRO A 144 30.269 14.765 −46.437 1.00 49.56 A ATOM 562 N GLY A 145 30.639 14.684 −44.216 1.00 48.72 A ATOM 563 CA GLY A 145 30.260 16.070 −44.010 1.00 50.25 A ATOM 564 C GLY A 145 29.010 16.538 −44.735 1.00 51.98 A ATOM 565 O GLY A 145 28.889 17.719 −45.063 1.00 51.37 A ATOM 566 N GLU A 146 28.074 15.625 −44.986 1.00 53.56 A ATOM 567 CA GLU A 146 26.834 15.989 −45.664 1.00 54.37 A ATOM 568 CB GLU A 146 26.947 15.734 −47.175 1.00 56.97 A ATOM 569 CG GLU A 146 25.797 16.333 −47.990 1.00 61.12 A ATOM 570 CD GLU A 146 25.915 16.063 −49.483 1.00 64.36 A ATOM 571 OE1 GLU A 146 25.957 14.876 −49.877 1.00 65.64 A ATOM 572 OE2 GLU A 146 25.961 17.040 −50.263 1.00 66.22 A ATOM 573 C GLU A 146 25.640 15.224 −45.099 1.00 52.66 A ATOM 574 O GLU A 146 24.731 14.850 −45.833 1.00 53.40 A ATOM 575 N GLY A 147 25.646 14.994 −43.790 1.00 51.08 A ATOM 576 CA GLY A 147 24.546 14.281 −43.167 1.00 48.20 A ATOM 577 C GLY A 147 24.567 14.368 −41.652 1.00 46.60 A ATOM 578 O GLY A 147 24.767 15.442 −41.080 1.00 46.48 A ATOM 579 N LYS A 148 24.361 13.230 −40.997 1.00 44.44 A ATOM 580 CA LYS A 148 24.353 13.171 −39.541 1.00 42.17 A ATOM 581 CB LYS A 148 22.908 13.167 −39.032 1.00 44.06 A ATOM 582 CG LYS A 148 22.653 13.989 −37.773 1.00 44.66 A ATOM 583 CD LYS A 148 23.184 13.323 −36.515 1.00 46.34 A ATOM 584 CE LYS A 148 22.674 14.052 −35.271 1.00 47.35 A ATOM 585 NZ LYS A 148 23.051 13.382 −33.995 1.00 48.38 A ATOM 586 C LYS A 148 25.064 11.889 −39.126 1.00 40.11 A ATOM 587 O LYS A 148 24.509 10.799 −39.251 1.00 39.43 A ATOM 588 N GLU A 149 26.297 12.020 −38.646 1.00 37.37 A ATOM 589 CA GLU A 149 27.062 10.853 −38.227 1.00 35.24 A ATOM 590 CB GLU A 149 28.559 11.133 −38.288 1.00 33.46 A ATOM 591 CG GLU A 149 29.049 11.512 −39.662 1.00 33.59 A ATOM 592 CD GLU A 149 30.535 11.306 −39.810 1.00 32.30 A ATOM 593 OE1 GLU A 149 31.252 11.517 −38.809 1.00 29.90 A ATOM 594 OE2 GLU A 149 30.982 10.943 −40.923 1.00 31.18 A ATOM 595 C GLU A 149 26.692 10.414 −36.823 1.00 33.65 A ATOM 596 O GLU A 149 26.843 11.169 −35.863 1.00 33.30 A ATOM 597 N ILE A 150 26.210 9.180 −36.715 1.00 31.34 A ATOM 598 CA ILE A 150 25.808 8.622 −35.434 1.00 28.27 A ATOM 599 CB ILE A 150 24.303 8.325 −35.411 1.00 28.74 A ATOM 600 CG2 ILE A 150 23.948 7.564 −34.138 1.00 27.91 A ATOM 601 CG1 ILE A 150 23.518 9.634 −35.538 1.00 29.27 A ATOM 602 CD1 ILE A 150 22.030 9.449 −35.777 1.00 31.15 A ATOM 603 C ILE A 150 26.541 7.326 −35.156 1.00 26.22 A ATOM 604 O ILE A 150 26.504 6.400 −35.965 1.00 27.50 A ATOM 605 N VAL A 151 27.218 7.265 −34.017 1.00 22.94 A ATOM 606 CA VAL A 151 27.931 6.057 −33.629 1.00 21.78 A ATOM 607 CB VAL A 151 29.468 6.322 −33.492 1.00 21.52 A ATOM 608 CG1 VAL A 151 29.748 7.803 −33.617 1.00 20.75 A ATOM 609 CG2 VAL A 151 30.001 5.774 −32.182 1.00 19.13 A ATOM 610 C VAL A 151 27.319 5.577 −32.316 1.00 20.78 A ATOM 611 O VAL A 151 26.936 6.390 −31.473 1.00 22.39 A ATOM 612 N LEU A 152 27.196 4.264 −32.152 1.00 19.13 A ATOM 613 CA LEU A 152 26.600 3.716 −30.938 1.00 19.50 A ATOM 614 CB LEU A 152 25.161 3.260 −31.223 1.00 19.10 A ATOM 615 CG LEU A 152 24.193 4.305 −31.798 1.00 24.16 A ATOM 616 CD1 LEU A 152 23.081 3.618 −32.569 1.00 24.32 A ATOM 617 CD2 LEU A 152 23.618 5.156 −30.677 1.00 24.79 A ATOM 618 C LEU A 152 27.392 2.545 −30.353 1.00 17.69 A ATOM 619 O LEU A 152 27.678 1.571 −31.049 1.00 16.33 A ATOM 620 N VAL A 153 27.742 2.641 −29.073 1.00 15.12 A ATOM 621 CA VAL A 153 28.466 1.563 −28.409 1.00 14.13 A ATOM 622 CB VAL A 153 29.672 2.096 −27.611 1.00 13.29 A ATOM 623 CG1 VAL A 153 30.442 0.939 −26.997 1.00 12.78 A ATOM 624 CG2 VAL A 153 30.578 2.901 −28.514 1.00 14.26 A ATOM 625 C VAL A 153 27.498 0.843 −27.457 1.00 15.36 A ATOM 626 O VAL A 153 26.748 1.491 −26.719 1.00 12.91 A ATOM 627 N ASN A 154 27.530 −0.492 −27.480 1.00 15.63 A ATOM 628 CA ASN A 154 26.653 −1.334 −26.658 1.00 16.94 A ATOM 629 CB ASN A 154 27.180 −1.448 −25.225 1.00 15.99 A ATOM 630 CG ASN A 154 28.646 −1.828 −25.171 1.00 17.69 A ATOM 631 OD1 ASN A 154 29.097 −2.698 −25.915 1.00 17.61 A ATOM 632 ND2 ASN A 154 29.398 −1.182 −24.282 1.00 15.37 A ATOM 633 C ASN A 154 25.216 −0.801 −26.632 1.00 17.66 A ATOM 634 O ASN A 154 24.666 −0.510 −25.571 1.00 17.48 A ATOM 635 N PRO A 155 24.588 −0.677 −27.814 1.00 18.56 A ATOM 636 CD PRO A 155 25.183 −0.907 −29.138 1.00 18.26 A ATOM 637 CA PRO A 155 23.215 −0.181 −27.950 1.00 18.44 A ATOM 638 CB PRO A 155 23.056 0.004 −29.459 1.00 17.65 A ATOM 639 CG PRO A 155 24.458 0.102 −29.966 1.00 19.09 A ATOM 640 C PRO A 155 22.173 −1.157 −27.412 1.00 18.75 A ATOM 641 O PRO A 155 22.277 −2.365 −27.606 1.00 19.82 A ATOM 642 N LYS A 156 21.162 −0.622 −26.745 1.00 20.00 A ATOM 643 CA LYS A 156 20.082 −1.441 −26.221 1.00 20.87 A ATOM 644 CB LYS A 156 20.150 −1.499 −24.701 1.00 21.41 A ATOM 645 CG LYS A 156 21.482 −1.949 −24.167 1.00 26.83 A ATOM 646 CD LYS A 156 21.488 −1.995 −22.637 1.00 30.30 A ATOM 647 CE LYS A 156 21.449 −0.601 −22.030 1.00 34.64 A ATOM 648 NZ LYS A 156 21.678 −0.636 −20.551 1.00 36.85 A ATOM 649 C LYS A 156 18.751 −0.824 −26.653 1.00 21.39 A ATOM 650 O LYS A 156 18.532 0.388 −26.514 1.00 19.74 A ATOM 651 N ILE A 157 17.869 −1.649 −27.198 1.00 22.00 A ATOM 652 CA ILE A 157 16.571 −1.148 −27.616 1.00 24.95 A ATOM 653 CB ILE A 157 15.983 −1.978 −28.781 1.00 24.61 A ATOM 654 CG2 ILE A 157 14.540 −1.559 −29.045 1.00 24.26 A ATOM 655 CG1 ILE A 157 16.834 −1.779 −30.038 1.00 24.91 A ATOM 656 CD1 ILE A 157 16.258 −2.433 −31.290 1.00 25.22 A ATOM 657 C ILE A 157 15.634 −1.204 −26.422 1.00 26.62 A ATOM 658 O ILE A 157 15.236 −2.284 −25.988 1.00 25.35 A ATOM 659 N LYS A 158 15.306 −0.035 −25.879 1.00 30.00 A ATOM 660 CA LYS A 158 14.411 0.052 −24.732 1.00 32.44 A ATOM 661 CB LYS A 158 14.584 1.393 −24.009 1.00 34.21 A ATOM 662 CG LYS A 158 15.822 1.460 −23.114 1.00 36.80 A ATOM 663 CD LYS A 158 15.721 0.464 −21.965 1.00 37.85 A ATOM 664 CE LYS A 158 17.089 0.107 −21.389 1.00 40.17 A ATOM 665 NZ LYS A 158 17.827 1.271 −20.817 1.00 40.51 A ATOM 666 C LYS A 158 12.969 −0.119 −25.170 1.00 32.94 A ATOM 667 O LYS A 158 12.183 −0.765 −24.486 1.00 34.80 A ATOM 668 N LYS A 159 12.623 0.456 −26.314 1.00 33.25 A ATOM 669 CA LYS A 159 11.269 0.349 −26.834 1.00 34.87 A ATOM 670 CB LYS A 159 10.367 1.438 −26.235 1.00 37.06 A ATOM 671 CG LYS A 159 10.126 1.305 −24.736 1.00 40.70 A ATOM 672 CD LYS A 159 9.057 2.265 −24.239 1.00 42.38 A ATOM 673 CE LYS A 159 8.687 1.963 −22.787 1.00 44.63 A ATOM 674 NZ LYS A 159 7.473 2.710 −22.322 1.00 46.12 A ATOM 675 C LYS A 159 11.269 0.495 −28.340 1.00 34.89 A ATOM 676 O LYS A 159 12.135 1.161 −28.903 1.00 35.59 A ATOM 677 N TYR A 160 10.311 −0.147 −28.996 1.00 35.44 A ATOM 678 CA TYR A 160 10.187 −0.025 −30.439 1.00 36.62 A ATOM 679 CB TYR A 160 10.842 −1.208 −31.162 1.00 42.19 A ATOM 680 CG TYR A 160 10.445 −2.569 −30.673 1.00 47.11 A ATOM 681 CD1 TYR A 160 9.143 −3.037 −30.838 1.00 50.34 A ATOM 682 CE1 TYR A 160 8.776 −4.314 −30.407 1.00 53.27 A ATOM 683 CD2 TYR A 160 11.381 −3.405 −30.062 1.00 49.07 A ATOM 684 CE2 TYR A 160 11.030 −4.677 −29.626 1.00 52.79 A ATOM 685 CZ TYR A 160 9.723 −5.129 −29.802 1.00 54.17 A ATOM 686 OH TYR A 160 9.363 −6.395 −29.381 1.00 56.97 A ATOM 687 C TYR A 160 8.718 0.129 −30.812 1.00 33.35 A ATOM 688 O TYR A 160 7.833 −0.296 −30.077 1.00 33.80 A ATOM 689 N SER A 161 8.469 0.770 −31.945 1.00 28.83 A ATOM 690 CA SER A 161 7.117 1.037 −32.406 1.00 25.47 A ATOM 691 CB SER A 161 7.175 1.761 −33.756 1.00 25.05 A ATOM 692 OG SER A 161 5.877 2.039 −34.248 1.00 25.20 A ATOM 693 C SER A 161 6.227 −0.194 −32.525 1.00 24.00 A ATOM 694 O SER A 161 6.699 −1.310 −32.736 1.00 25.13 A ATOM 695 N ASP A 162 4.927 0.016 −32.377 1.00 20.81 A ATOM 696 CA ASP A 162 3.988 −1.078 −32.512 1.00 18.67 A ATOM 697 CB ASP A 162 2.924 −1.012 −31.404 1.00 17.74 A ATOM 698 CG ASP A 162 2.043 0.224 −31.491 1.00 20.48 A ATOM 699 OD1 ASP A 162 2.411 1.197 −32.193 1.00 19.28 A ATOM 700 OD2 ASP A 162 0.974 0.216 −30.832 1.00 20.44 A ATOM 701 C ASP A 162 3.361 −1.031 −33.917 1.00 17.19 A ATOM 702 O ASP A 162 2.405 −1.748 −34.214 1.00 16.88 A ATOM 703 N LYS A 163 3.922 −0.185 −34.778 1.00 13.19 A ATOM 704 CA LYS A 163 3.458 −0.060 −36.157 1.00 14.42 A ATOM 705 CB LYS A 163 3.063 1.392 −36.465 1.00 17.11 A ATOM 706 CG LYS A 163 2.008 1.943 −35.516 1.00 21.55 A ATOM 707 CD LYS A 163 1.511 3.321 −35.933 1.00 25.69 A ATOM 708 CE LYS A 163 0.470 3.836 −34.942 1.00 26.67 A ATOM 709 NZ LYS A 163 −0.163 5.115 −35.373 1.00 30.99 A ATOM 710 C LYS A 163 4.563 −0.515 −37.114 1.00 14.12 A ATOM 711 O LYS A 163 5.709 −0.067 −37.029 1.00 11.38 A ATOM 712 N LEU A 164 4.207 −1.405 −38.032 1.00 14.88 A ATOM 713 CA LEU A 164 5.167 −1.934 −38.987 1.00 15.75 A ATOM 714 CB LEU A 164 4.933 −3.430 −39.182 1.00 16.05 A ATOM 715 CG LEU A 164 5.202 −4.299 −37.953 1.00 17.46 A ATOM 716 CD1 LEU A 164 4.720 −5.716 −38.219 1.00 15.64 A ATOM 717 CD2 LEU A 164 6.696 −4.269 −37.617 1.00 16.61 A ATOM 718 C LEU A 164 5.153 −1.251 −40.340 1.00 17.09 A ATOM 719 O LEU A 164 4.097 −0.893 −40.865 1.00 17.75 A ATOM 720 N VAL A 165 6.343 −1.066 −40.900 1.00 17.38 A ATOM 721 CA VAL A 165 6.466 −0.457 −42.209 1.00 18.26 A ATOM 722 CB VAL A 165 6.899 1.017 −42.118 1.00 16.51 A ATOM 723 CG1 VAL A 165 5.763 1.841 −41.511 1.00 16.42 A ATOM 724 CG2 VAL A 165 8.172 1.145 −41.290 1.00 17.21 A ATOM 725 C VAL A 165 7.469 −1.243 −43.045 1.00 19.14 A ATOM 726 O VAL A 165 8.433 −1.808 −42.518 1.00 20.01 A ATOM 727 N PRO A 166 7.234 −1.316 −44.362 1.00 19.02 A ATOM 728 CD PRO A 166 5.982 −0.965 −45.062 1.00 18.32 A ATOM 729 CA PRO A 166 8.137 −2.047 −45.251 1.00 20.65 A ATOM 730 CB PRO A 166 7.195 −2.543 −46.340 1.00 20.89 A ATOM 731 CG PRO A 166 6.284 −1.350 −46.503 1.00 19.48 A ATOM 732 C PRO A 166 9.222 −1.132 −45.805 1.00 21.42 A ATOM 733 O PRO A 166 9.073 0.087 −45.803 1.00 21.01 A ATOM 734 N PHE A 167 10.312 −1.728 −46.275 1.00 23.28 A ATOM 735 CA PHE A 167 11.405 −0.966 −46.859 1.00 25.18 A ATOM 736 CB PHE A 167 12.141 −0.176 −45.779 1.00 28.27 A ATOM 737 CG PHE A 167 13.095 0.840 −46.325 1.00 33.26 A ATOM 738 CD1 PHE A 167 12.637 2.083 −46.751 1.00 35.31 A ATOM 739 CD2 PHE A 167 14.450 0.540 −46.459 1.00 36.84 A ATOM 740 CE1 PHE A 167 13.514 3.022 −47.308 1.00 37.46 A ATOM 741 CE2 PHE A 167 15.341 1.468 −47.014 1.00 38.88 A ATOM 742 CZ PHE A 167 14.870 2.714 −47.440 1.00 38.07 A ATOM 743 C PHE A 167 12.375 −1.919 −47.547 1.00 24.62 A ATOM 744 O PHE A 167 12.677 −2.981 −47.010 1.00 24.38 A ATOM 745 N ASP A 168 12.837 −1.562 −48.745 1.00 25.04 A ATOM 746 CA ASP A 168 13.791 −2.414 −49.456 1.00 25.00 A ATOM 747 CB ASP A 168 13.804 −2.116 −50.958 1.00 27.03 A ATOM 748 CG ASP A 168 12.478 −2.418 −51.629 1.00 28.34 A ATOM 749 OD1 ASP A 168 11.679 −3.193 −51.063 1.00 30.93 A ATOM 750 OD2 ASP A 168 12.239 −1.890 −52.736 1.00 31.05 A ATOM 751 C ASP A 168 15.155 −2.113 −48.861 1.00 24.01 A ATOM 752 O ASP A 168 15.679 −1.010 −49.002 1.00 23.88 A ATOM 753 N GLU A 169 15.723 −3.095 −48.182 1.00 23.69 A ATOM 754 CA GLU A 169 17.011 −2.908 −47.532 1.00 23.00 A ATOM 755 CB GLU A 169 16.997 −3.555 −46.149 1.00 23.01 A ATOM 756 CG GLU A 169 16.073 −2.907 −45.142 1.00 24.80 A ATOM 757 CD GLU A 169 16.034 −3.679 −43.833 1.00 25.40 A ATOM 758 OE1 GLU A 169 17.108 −4.145 −43.398 1.00 24.55 A ATOM 759 OE2 GLU A 169 14.940 −3.814 −43.240 1.00 25.14 A ATOM 760 C GLU A 169 18.182 −3.478 −48.305 1.00 21.78 A ATOM 761 O GLU A 169 18.068 −4.495 −48.979 1.00 21.39 A ATOM 762 N GLY A 170 19.312 −2.797 −48.196 1.00 20.18 A ATOM 763 CA GLY A 170 20.526 −3.262 −48.826 1.00 19.41 A ATOM 764 C GLY A 170 21.488 −3.541 −47.684 1.00 19.42 A ATOM 765 O GLY A 170 21.205 −3.179 −46.533 1.00 18.09 A ATOM 766 N CYS A 171 22.609 −4.189 −47.983 1.00 17.85 A ATOM 767 CA CYS A 171 23.617 −4.495 −46.973 1.00 17.78 A ATOM 768 CB CYS A 171 23.274 −5.793 −46.222 1.00 17.35 A ATOM 769 SG CYS A 171 24.482 −6.273 −44.946 1.00 17.05 A ATOM 770 C CYS A 171 24.956 −4.644 −47.667 1.00 17.66 A ATOM 771 O CYS A 171 25.051 −5.264 −48.731 1.00 18.62 A ATOM 772 N LEU A 172 25.988 −4.071 −47.060 1.00 18.65 A ATOM 773 CA LEU A 172 27.337 −4.120 −47.607 1.00 17.51 A ATOM 774 CB LEU A 172 28.268 −3.218 −46.780 1.00 18.35 A ATOM 775 CG LEU A 172 28.433 −1.739 −47.177 1.00 18.16 A ATOM 776 CD1 LEU A 172 27.382 −1.317 −48.180 1.00 19.26 A ATOM 777 CD2 LEU A 172 28.373 −0.875 −45.930 1.00 17.19 A ATOM 778 C LEU A 172 27.895 −5.537 −47.672 1.00 17.16 A ATOM 779 O LEU A 172 28.819 −5.811 −48.438 1.00 19.43 A ATOM 780 N SER A 173 27.335 −6.442 −46.879 1.00 15.56 A ATOM 781 CA SER A 173 27.807 −7.822 −46.880 1.00 15.09 A ATOM 782 CB SER A 173 27.627 −8.438 −45.498 1.00 13.35 A ATOM 783 OG SER A 173 28.432 −7.766 −44.542 1.00 13.38 A ATOM 784 C SER A 173 27.077 −8.668 −47.920 1.00 16.25 A ATOM 785 O SER A 173 27.318 −9.872 −48.037 1.00 16.75 A ATOM 786 N PHE A 174 26.180 −8.029 −48.664 1.00 16.57 A ATOM 787 CA PHE A 174 25.396 −8.688 −49.709 1.00 17.10 A ATOM 788 CB PHE A 174 23.954 −8.905 −49.235 1.00 18.18 A ATOM 789 CG PHE A 174 23.819 −9.875 −48.085 1.00 17.61 A ATOM 790 CD1 PHE A 174 23.432 −11.196 −48.313 1.00 17.43 A ATOM 791 CD2 PHE A 174 24.047 −9.461 −46.775 1.00 18.73 A ATOM 792 CE1 PHE A 174 23.267 −12.091 −47.253 1.00 16.70 A ATOM 793 CE2 PHE A 174 23.887 −10.352 −45.703 1.00 19.19 A ATOM 794 CZ PHE A 174 23.495 −11.670 −45.946 1.00 18.29 A ATOM 795 C PHE A 174 25.413 −7.748 −50.916 1.00 16.80 A ATOM 796 O PHE A 174 24.402 −7.142 −51.276 1.00 16.00 A ATOM 797 N PRO A 175 26.576 −7.627 −51.562 1.00 18.42 A ATOM 798 CD PRO A 175 27.766 −8.470 −51.335 1.00 17.82 A ATOM 799 CA PRO A 175 26.771 −6.762 −52.728 1.00 19.70 A ATOM 800 CB PRO A 175 28.048 −7.317 −53.350 1.00 20.05 A ATOM 801 CG PRO A 175 28.826 −7.755 −52.138 1.00 18.23 A ATOM 802 C PRO A 175 25.617 −6.700 −53.716 1.00 20.20 A ATOM 803 O PRO A 175 25.240 −7.710 −54.312 1.00 20.33 A ATOM 804 N GLY A 176 25.059 −5.497 −53.866 1.00 21.23 A ATOM 805 CA GLY A 176 23.968 −5.260 −54.800 1.00 19.68 A ATOM 806 C GLY A 176 22.669 −6.019 −54.598 1.00 18.84 A ATOM 807 O GLY A 176 21.826 −6.065 −55.498 1.00 16.30 A ATOM 808 N ILE A 177 22.487 −6.621 −53.430 1.00 18.40 A ATOM 809 CA ILE A 177 21.256 −7.355 −53.186 1.00 19.40 A ATOM 810 CB ILE A 177 21.547 −8.683 −52.450 1.00 19.34 A ATOM 811 CG2 ILE A 177 20.250 −9.372 −52.066 1.00 20.31 A ATOM 812 CG1 ILE A 177 22.398 −9.584 −53.352 1.00 20.29 A ATOM 813 CD1 ILE A 177 22.776 −10.927 −52.735 1.00 18.41 A ATOM 814 C ILE A 177 20.278 −6.498 −52.391 1.00 19.23 A ATOM 815 O ILE A 177 20.642 −5.904 −51.378 1.00 18.56 A ATOM 816 N TYR A 178 19.043 −6.408 −52.878 1.00 20.54 A ATOM 817 CA TYR A 178 18.014 −5.624 −52.199 1.00 22.95 A ATOM 818 CB TYR A 178 17.813 −4.266 −52.879 1.00 24.10 A ATOM 819 CG TYR A 178 19.064 −3.420 −52.962 1.00 27.38 A ATOM 820 CD1 TYR A 178 20.069 −3.721 −53.888 1.00 26.85 A ATOM 821 CE1 TYR A 178 21.235 −2.962 −53.962 1.00 27.02 A ATOM 822 CD2 TYR A 178 19.258 −2.330 −52.106 1.00 26.90 A ATOM 823 CE2 TYR A 178 20.431 −1.560 −52.176 1.00 28.14 A ATOM 824 CZ TYR A 178 21.414 −1.888 −53.111 1.00 28.84 A ATOM 825 OH TYR A 178 22.577 −1.147 −53.210 1.00 30.05 A ATOM 826 C TYR A 178 16.680 −6.352 −52.154 1.00 22.69 A ATOM 827 O TYR A 178 16.192 −6.839 −53.175 1.00 23.47 A ATOM 828 N ALA A 179 16.095 −6.430 −50.965 1.00 21.13 A ATOM 829 CA ALA A 179 14.801 −7.085 −50.800 1.00 21.16 A ATOM 830 CB ALA A 179 14.991 −8.557 −50.478 1.00 20.57 A ATOM 831 C ALA A 179 14.021 −6.390 −49.697 1.00 21.14 A ATOM 832 O ALA A 179 14.597 −5.699 −48.855 1.00 21.11 A ATOM 833 N GLU A 180 12.706 −6.569 −49.706 1.00 21.61 A ATOM 834 CA GLU A 180 11.842 −5.929 −48.721 1.00 22.07 A ATOM 835 CB GLU A 180 10.399 −5.943 −49.230 1.00 24.22 A ATOM 836 CG GLU A 180 9.437 −5.163 −48.352 1.00 27.20 A ATOM 837 CD GLU A 180 8.021 −5.150 −48.893 1.00 27.70 A ATOM 838 OE1 GLU A 180 7.245 −6.075 −48.568 1.00 27.79 A ATOM 839 OE2 GLU A 180 7.691 −4.210 −49.649 1.00 27.64 A ATOM 840 C GLU A 180 11.880 −6.526 −47.306 1.00 20.52 A ATOM 841 O GLU A 180 11.805 −7.736 −47.124 1.00 20.89 A ATOM 842 N VAL A 181 11.993 −5.664 −46.304 1.00 19.74 A ATOM 843 CA VAL A 181 11.995 −6.112 −44.916 1.00 20.39 A ATOM 844 CB VAL A 181 13.399 −5.964 −44.264 1.00 20.82 A ATOM 845 CG1 VAL A 181 13.372 −6.508 −42.840 1.00 20.17 A ATOM 846 CG2 VAL A 181 14.450 −6.708 −45.089 1.00 18.51 A ATOM 847 C VAL A 181 10.984 −5.268 −44.136 1.00 20.46 A ATOM 848 O VAL A 181 10.877 −4.063 −44.352 1.00 20.70 A ATOM 849 N VAL A 182 10.224 −5.901 −43.248 1.00 20.35 A ATOM 850 CA VAL A 182 9.235 −5.183 −42.443 1.00 19.16 A ATOM 851 CB VAL A 182 7.881 −5.935 −42.419 1.00 20.20 A ATOM 852 CG1 VAL A 182 6.865 −5.168 −41.587 1.00 19.98 A ATOM 853 CG2 VAL A 182 7.365 −6.120 −43.841 1.00 20.58 A ATOM 854 C VAL A 182 9.738 −5.020 −41.011 1.00 17.95 A ATOM 855 O VAL A 182 10.083 −6.001 −40.353 1.00 18.95 A ATOM 856 N ARG A 183 9.789 −3.781 −40.531 1.00 16.50 A ATOM 857 CA ARG A 183 10.257 −3.516 −39.169 1.00 14.82 A ATOM 858 CB ARG A 183 11.713 −3.036 −39.167 1.00 15.48 A ATOM 859 CG ARG A 183 12.749 −3.901 −39.862 1.00 12.14 A ATOM 860 CD ARG A 183 14.098 −3.199 −39.730 1.00 13.95 A ATOM 861 NE ARG A 183 15.172 −3.826 −40.492 1.00 14.27 A ATOM 862 CZ ARG A 183 15.907 −4.844 −40.062 1.00 14.82 A ATOM 863 NH1 ARG A 183 15.687 −5.361 −38.856 1.00 13.88 A ATOM 864 NH2 ARG A 183 16.863 −5.342 −40.845 1.00 10.27 A ATOM 865 C ARG A 183 9.436 −2.421 −38.502 1.00 15.01 A ATOM 866 O ARG A 183 8.731 −1.658 −39.172 1.00 13.85 A ATOM 867 N PRO A 184 9.512 −2.332 −37.161 1.00 14.58 A ATOM 868 CD PRO A 184 10.141 −3.264 −36.206 1.00 13.75 A ATOM 869 CA PRO A 184 8.764 −1.285 −36.458 1.00 14.05 A ATOM 870 CB PRO A 184 9.171 −1.496 −35.001 1.00 13.48 A ATOM 871 CG PRO A 184 9.379 −2.981 −34.926 1.00 13.61 A ATOM 872 C PRO A 184 9.287 0.035 −37.030 1.00 13.54 A ATOM 873 O PRO A 184 10.463 0.123 −37.394 1.00 12.47 A ATOM 874 N GLN A 185 8.437 1.052 −37.121 1.00 14.24 A ATOM 875 CA GLN A 185 8.867 2.326 −37.703 1.00 16.35 A ATOM 876 CB GLN A 185 7.647 3.160 −38.144 1.00 16.49 A ATOM 877 CG GLN A 185 6.647 3.488 −37.053 1.00 18.19 A ATOM 878 CD GLN A 185 5.486 4.339 −37.562 1.00 20.93 A ATOM 879 OE1 GLN A 185 5.126 4.276 −38.735 1.00 22.48 A ATOM 880 NE2 GLN A 185 4.886 5.126 −36.672 1.00 19.77 A ATOM 881 C GLN A 185 9.783 3.191 −36.843 1.00 16.52 A ATOM 882 O GLN A 185 10.467 4.071 −37.358 1.00 16.86 A ATOM 883 N SER A 186 9.804 2.951 −35.540 1.00 17.54 A ATOM 884 CA SER A 186 10.642 3.749 −34.655 1.00 17.28 A ATOM 885 CB SER A 186 9.888 4.984 −34.193 1.00 16.83 A ATOM 886 OG SER A 186 8.814 4.597 −33.365 1.00 16.18 A ATOM 887 C SER A 186 11.087 2.963 −33.433 1.00 18.56 A ATOM 888 O SER A 186 10.483 1.948 −33.072 1.00 17.15 A ATOM 889 N VAL A 187 12.145 3.454 −32.794 1.00 18.41 A ATOM 890 CA VAL A 187 12.707 2.812 −31.614 1.00 17.19 A ATOM 891 CB VAL A 187 13.880 1.875 −31.990 1.00 16.71 A ATOM 892 CG1 VAL A 187 13.376 0.651 −32.717 1.00 14.52 A ATOM 893 CG2 VAL A 187 14.868 2.629 −32.869 1.00 16.52 A ATOM 894 C VAL A 187 13.257 3.845 −30.643 1.00 19.68 A ATOM 895 O VAL A 187 13.471 5.012 −30.991 1.00 17.36 A ATOM 896 N LYS A 188 13.488 3.379 −29.422 1.00 22.44 A ATOM 897 CA LYS A 188 14.041 4.170 −28.333 1.00 24.50 A ATOM 898 CB LYS A 188 13.044 4.223 −27.175 1.00 27.86 A ATOM 899 CG LYS A 188 13.634 4.704 −25.858 1.00 32.55 A ATOM 900 CD LYS A 188 12.604 4.645 −24.724 1.00 37.24 A ATOM 901 CE LYS A 188 11.438 5.613 −24.952 1.00 39.23 A ATOM 902 NZ LYS A 188 10.474 5.621 −23.803 1.00 40.21 A ATOM 903 C LYS A 188 15.291 3.399 −27.925 1.00 24.24 A ATOM 904 O LYS A 188 15.202 2.222 −27.574 1.00 25.34 A ATOM 905 N ILE A 189 16.449 4.049 −27.976 1.00 25.02 A ATOM 906 CA ILE A 189 17.707 3.382 −27.648 1.00 25.74 A ATOM 907 CB ILE A 189 18.677 3.413 −28.853 1.00 25.43 A ATOM 908 CG2 ILE A 189 19.959 2.665 −28.520 1.00 27.70 A ATOM 909 CG1 ILE A 189 18.010 2.801 −30.084 1.00 25.02 A ATOM 910 CD1 ILE A 189 17.209 3.794 −30.886 1.00 26.73 A ATOM 911 C ILE A 189 18.476 3.936 −26.452 1.00 26.55 A ATOM 912 O ILE A 189 18.340 5.098 −26.080 1.00 28.56 A ATOM 913 N ASP A 190 19.296 3.071 −25.867 1.00 26.77 A ATOM 914 CA ASP A 190 20.167 3.398 −24.745 1.00 25.30 A ATOM 915 CB ASP A 190 19.769 2.591 −23.506 1.00 27.91 A ATOM 916 CG ASP A 190 19.126 3.447 −22.425 1.00 29.11 A ATOM 917 OD1 ASP A 190 18.312 4.335 −22.757 1.00 32.09 A ATOM 918 OD2 ASP A 190 19.428 3.220 −21.235 1.00 31.65 A ATOM 919 C ASP A 190 21.527 2.930 −25.249 1.00 23.53 A ATOM 920 O ASP A 190 21.631 1.846 −25.814 1.00 25.23 A ATOM 921 N ALA A 191 22.564 3.735 −25.073 1.00 20.98 A ATOM 922 CA ALA A 191 23.889 3.339 −25.536 1.00 19.22 A ATOM 923 CB ALA A 191 23.975 3.501 −27.052 1.00 16.43 A ATOM 924 C ALA A 191 24.961 4.179 −24.869 1.00 16.73 A ATOM 925 O ALA A 191 24.659 5.021 −24.031 1.00 14.46 A ATOM 926 N ARG A 192 26.215 3.932 −25.241 1.00 17.62 A ATOM 927 CA ARG A 192 27.344 4.701 −24.719 1.00 16.89 A ATOM 928 CB ARG A 192 28.344 3.813 −23.983 1.00 14.64 A ATOM 929 CG ARG A 192 27.849 3.112 −22.736 1.00 16.43 A ATOM 930 CD ARG A 192 28.933 2.152 −22.266 1.00 14.30 A ATOM 931 NE ARG A 192 28.564 1.361 −21.099 1.00 17.12 A ATOM 932 CZ ARG A 192 28.434 1.847 −19.868 1.00 17.79 A ATOM 933 NH1 ARG A 192 28.638 3.137 −19.629 1.00 18.41 A ATOM 934 NH2 ARG A 192 28.116 1.035 −18.869 1.00 16.93 A ATOM 935 C ARG A 192 28.060 5.305 −25.921 1.00 16.09 A ATOM 936 O ARG A 192 27.943 4.800 −27.029 1.00 14.43 A ATOM 937 N ASP A 193 28.808 6.378 −25.691 1.00 17.73 A ATOM 938 CA ASP A 193 29.574 7.023 −26.750 1.00 19.68 A ATOM 939 CB ASP A 193 29.559 8.543 −26.557 1.00 21.17 A ATOM 940 CG ASP A 193 30.420 8.997 −25.394 1.00 22.73 A ATOM 941 OD1 ASP A 193 30.523 8.270 −24.381 1.00 23.37 A ATOM 942 OD2 ASP A 193 30.991 10.101 −25.493 1.00 26.89 A ATOM 943 C ASP A 193 30.997 6.462 −26.634 1.00 19.97 A ATOM 944 O ASP A 193 31.235 5.571 −25.815 1.00 17.40 A ATOM 945 N ILE A 194 31.937 6.971 −27.430 1.00 20.45 A ATOM 946 CA ILE A 194 33.304 6.451 −27.385 1.00 21.45 A ATOM 947 CB ILE A 194 34.173 6.962 −28.554 1.00 21.84 A ATOM 948 CG2 ILE A 194 33.679 6.381 −29.862 1.00 22.88 A ATOM 949 CG1 ILE A 194 34.180 8.488 −28.592 1.00 22.27 A ATOM 950 CD1 ILE A 194 35.136 9.058 −29.644 1.00 23.29 A ATOM 951 C ILE A 194 34.057 6.732 −26.093 1.00 22.29 A ATOM 952 O ILE A 194 35.073 6.098 −25.824 1.00 23.35 A ATOM 953 N THR A 195 33.574 7.676 −25.292 1.00 21.53 A ATOM 954 CA THR A 195 34.248 7.978 −24.035 1.00 22.32 A ATOM 955 CB THR A 195 34.119 9.478 −23.636 1.00 21.72 A ATOM 956 OG1 THR A 195 32.741 9.811 −23.418 1.00 18.57 A ATOM 957 CG2 THR A 195 34.694 10.370 −24.723 1.00 20.26 A ATOM 958 C THR A 195 33.632 7.118 −22.941 1.00 22.63 A ATOM 959 O THR A 195 34.074 7.143 −21.791 1.00 21.86 A ATOM 960 N GLY A 196 32.601 6.363 −23.313 1.00 23.03 A ATOM 961 CA GLY A 196 31.930 5.493 −22.365 1.00 23.21 A ATOM 962 C GLY A 196 30.759 6.147 −21.660 1.00 24.01 A ATOM 963 O GLY A 196 30.146 5.535 −20.792 1.00 23.82 A ATOM 964 N GLU A 197 30.445 7.389 −22.019 1.00 26.36 A ATOM 965 CA GLU A 197 29.325 8.080 −21.391 1.00 27.87 A ATOM 966 CB GLU A 197 29.437 9.598 −21.558 1.00 30.06 A ATOM 967 CG GLU A 197 30.667 10.225 −20.908 1.00 35.75 A ATOM 968 CD GLU A 197 30.787 9.923 −19.420 1.00 39.16 A ATOM 969 OE1 GLU A 197 31.824 10.299 −18.825 1.00 42.10 A ATOM 970 OE2 GLU A 197 29.857 9.312 −18.844 1.00 39.72 A ATOM 971 C GLU A 197 28.037 7.593 −22.020 1.00 27.80 A ATOM 972 O GLU A 197 27.955 7.420 −23.236 1.00 28.26 A ATOM 973 N ARG A 198 27.031 7.365 −21.189 1.00 28.14 A ATOM 974 CA ARG A 198 25.753 6.885 −21.682 1.00 28.82 A ATOM 975 CB ARG A 198 24.991 6.185 −20.561 1.00 32.41 A ATOM 976 CG ARG A 198 25.853 5.255 −19.720 1.00 37.31 A ATOM 977 CD ARG A 198 25.068 4.036 −19.282 1.00 42.63 A ATOM 978 NE ARG A 198 24.541 3.322 −20.444 1.00 46.58 A ATOM 979 CZ ARG A 198 24.024 2.100 −20.403 1.00 48.75 A ATOM 980 NH1 ARG A 198 23.964 1.445 −19.247 1.00 48.98 A ATOM 981 NH2 ARG A 198 23.564 1.535 −21.518 1.00 48.98 A ATOM 982 C ARG A 198 24.900 8.016 −22.243 1.00 27.54 A ATOM 983 O ARG A 198 25.071 9.189 −21.891 1.00 27.87 A ATOM 984 N PHE A 199 23.986 7.653 −23.132 1.00 25.20 A ATOM 985 CA PHE A 199 23.079 8.613 −23.728 1.00 23.21 A ATOM 986 CB PHE A 199 23.769 9.393 −24.858 1.00 21.17 A ATOM 987 CG PHE A 199 24.088 8.572 −26.084 1.00 19.11 A ATOM 988 CD1 PHE A 199 23.124 8.359 −27.070 1.00 17.06 A ATOM 989 CD2 PHE A 199 25.373 8.049 −26.273 1.00 18.18 A ATOM 990 CE1 PHE A 199 23.437 7.639 −28.232 1.00 17.14 A ATOM 991 CE2 PHE A 199 25.698 7.328 −27.425 1.00 14.22 A ATOM 992 CZ PHE A 199 24.731 7.124 −28.407 1.00 16.27 A ATOM 993 C PHE A 199 21.859 7.871 −24.243 1.00 23.72 A ATOM 994 O PHE A 199 21.898 6.659 −24.450 1.00 21.75 A ATOM 995 N SER A 200 20.769 8.600 −24.431 1.00 25.35 A ATOM 996 CA SER A 200 19.541 8.000 −24.915 1.00 26.06 A ATOM 997 CB SER A 200 18.551 7.844 −23.767 1.00 26.35 A ATOM 998 OG SER A 200 19.115 7.060 −22.732 1.00 29.16 A ATOM 999 C SER A 200 18.941 8.867 −25.996 1.00 26.17 A ATOM 1000 O SER A 200 18.994 10.092 −25.915 1.00 27.31 A ATOM 1001 N ILE A 201 18.376 8.226 −27.013 1.00 26.58 A ATOM 1002 CA ILE A 201 17.756 8.942 −28.118 1.00 26.23 A ATOM 1003 CB ILE A 201 18.762 9.214 −29.250 1.00 28.26 A ATOM 1004 CG2 ILE A 201 19.813 10.216 −28.790 1.00 29.33 A ATOM 1005 CG1 ILE A 201 19.394 7.895 −29.701 1.00 28.98 A ATOM 1006 CD1 ILE A 201 20.230 8.010 −30.962 1.00 31.66 A ATOM 1007 C ILE A 201 16.593 8.152 −28.709 1.00 25.11 A ATOM 1008 O ILE A 201 16.418 6.958 −28.434 1.00 23.45 A ATOM 1009 N SER A 202 15.796 8.833 −29.522 1.00 24.09 A ATOM 1010 CA SER A 202 14.657 8.209 −30.180 1.00 23.76 A ATOM 1011 CB SER A 202 13.356 8.918 −29.802 1.00 23.27 A ATOM 1012 OG SER A 202 13.018 8.677 −28.447 1.00 26.12 A ATOM 1013 C SER A 202 14.864 8.297 −31.676 1.00 22.76 A ATOM 1014 O SER A 202 15.181 9.357 −32.205 1.00 20.95 A ATOM 1015 N LEU A 203 14.708 7.178 −32.364 1.00 22.93 A ATOM 1016 CA LEU A 203 14.871 7.193 −33.804 1.00 23.93 A ATOM 1017 CB LEU A 203 16.005 6.257 −34.237 1.00 23.48 A ATOM 1018 CG LEU A 203 17.387 6.575 −33.669 1.00 23.22 A ATOM 1019 CD1 LEU A 203 18.414 5.669 −34.321 1.00 23.21 A ATOM 1020 CD2 LEU A 203 17.727 8.039 −33.914 1.00 21.89 A ATOM 1021 C LEU A 203 13.585 6.795 −34.498 1.00 23.86 A ATOM 1022 O LEU A 203 12.781 6.024 −33.966 1.00 24.42 A ATOM 1023 N SER A 204 13.396 7.350 −35.685 1.00 25.11 A ATOM 1024 CA SER A 204 12.237 7.060 −36.514 1.00 27.28 A ATOM 1025 CB SER A 204 11.111 8.051 −36.236 1.00 28.55 A ATOM 1026 OG SER A 204 11.482 9.351 −36.658 1.00 30.10 A ATOM 1027 C SER A 204 12.741 7.248 −37.934 1.00 27.55 A ATOM 1028 O SER A 204 13.933 7.502 −38.137 1.00 27.70 A ATOM 1029 N ARG A 205 11.845 7.133 −38.910 1.00 28.31 A ATOM 1030 CA ARG A 205 12.221 7.315 −40.307 1.00 28.06 A ATOM 1031 CB ARG A 205 12.594 8.777 −40.569 1.00 31.86 A ATOM 1032 CG ARG A 205 11.428 9.756 −40.709 1.00 36.98 A ATOM 1033 CD ARG A 205 11.988 11.169 −40.867 1.00 40.88 A ATOM 1034 NE ARG A 205 11.122 12.070 −41.621 1.00 44.32 A ATOM 1035 CZ ARG A 205 11.423 13.343 −41.879 1.00 47.87 A ATOM 1036 NH1 ARG A 205 12.568 13.861 −41.442 1.00 48.05 A ATOM 1037 NH2 ARG A 205 10.583 14.107 −42.573 1.00 48.10 A ATOM 1038 C ARG A 205 13.396 6.424 −40.706 1.00 25.68 A ATOM 1039 O ARG A 205 13.523 5.293 −40.235 1.00 24.48 A ATOM 1040 N LEU A 206 14.261 6.958 −41.563 1.00 21.87 A ATOM 1041 CA LEU A 206 15.413 6.219 −42.057 1.00 19.85 A ATOM 1042 CB LEU A 206 16.115 7.006 −43.166 1.00 20.52 A ATOM 1043 CG LEU A 206 17.278 6.277 −43.856 1.00 23.37 A ATOM 1044 CD1 LEU A 206 16.765 5.016 −44.565 1.00 20.22 A ATOM 1045 CD2 LEU A 206 17.951 7.217 −44.853 1.00 22.79 A ATOM 1046 C LEU A 206 16.420 5.854 −40.974 1.00 18.21 A ATOM 1047 O LEU A 206 16.921 4.727 −40.953 1.00 16.21 A ATOM 1048 N PRO A 207 16.742 6.799 −40.069 1.00 16.71 A ATOM 1049 CD PRO A 207 16.439 8.245 −40.087 1.00 17.35 A ATOM 1050 CA PRO A 207 17.709 6.487 −39.008 1.00 17.46 A ATOM 1051 CB PRO A 207 17.795 7.794 −38.217 1.00 16.29 A ATOM 1052 CG PRO A 207 17.588 8.828 −39.283 1.00 16.84 A ATOM 1053 C PRO A 207 17.264 5.305 −38.154 1.00 16.91 A ATOM 1054 O PRO A 207 18.084 4.484 −37.747 1.00 18.14 A ATOM 1055 N ALA A 208 15.963 5.212 −37.896 1.00 16.46 A ATOM 1056 CA ALA A 208 15.437 4.106 −37.104 1.00 15.91 A ATOM 1057 CB ALA A 208 13.967 4.344 −36.780 1.00 16.38 A ATOM 1058 C ALA A 208 15.597 2.800 −37.883 1.00 14.15 A ATOM 1059 O ALA A 208 15.932 1.763 −37.320 1.00 14.30 A ATOM 1060 N ARG A 209 15.357 2.862 −39.187 1.00 14.77 A ATOM 1061 CA ARG A 209 15.473 1.686 −40.041 1.00 14.78 A ATOM 1062 CB ARG A 209 14.910 1.999 −41.434 1.00 16.76 A ATOM 1063 CG ARG A 209 14.841 0.804 −42.360 1.00 18.33 A ATOM 1064 CD ARG A 209 14.418 −0.437 −41.596 1.00 22.27 A ATOM 1065 NE ARG A 209 13.889 −1.463 −42.480 1.00 25.66 A ATOM 1066 CZ ARG A 209 12.611 −1.556 −42.834 1.00 28.46 A ATOM 1067 NH1 ARG A 209 11.709 −0.687 −42.377 1.00 27.84 A ATOM 1068 NH2 ARG A 209 12.235 −2.516 −43.659 1.00 28.08 A ATOM 1069 C ARG A 209 16.934 1.210 −40.145 1.00 14.81 A ATOM 1070 O ARG A 209 17.224 0.025 −40.001 1.00 12.46 A ATOM 1071 N ILE A 210 17.854 2.137 −40.389 1.00 13.90 A ATOM 1072 CA ILE A 210 19.261 1.774 −40.482 1.00 13.38 A ATOM 1073 CB ILE A 210 20.138 3.010 −40.830 1.00 14.75 A ATOM 1074 CG2 ILE A 210 21.620 2.649 −40.768 1.00 13.71 A ATOM 1075 CG1 ILE A 210 19.775 3.526 −42.229 1.00 12.89 A ATOM 1076 CD1 ILE A 210 20.449 4.828 −42.600 1.00 11.08 A ATOM 1077 C ILE A 210 19.709 1.200 −39.140 1.00 14.16 A ATOM 1078 O ILE A 210 20.444 0.210 −39.092 1.00 12.22 A ATOM 1079 N PHE A 211 19.247 1.816 −38.050 1.00 13.33 A ATOM 1080 CA PHE A 211 19.622 1.358 −36.718 1.00 13.42 A ATOM 1081 CB PHE A 211 18.978 2.221 −35.634 1.00 13.55 A ATOM 1082 CG PHE A 211 19.137 1.642 −34.261 1.00 10.76 A ATOM 1083 CD1 PHE A 211 20.323 1.815 −33.555 1.00 10.51 A ATOM 1084 CD2 PHE A 211 18.145 0.827 −33.719 1.00 11.87 A ATOM 1085 CE1 PHE A 211 20.522 1.175 −32.328 1.00 11.75 A ATOM 1086 CE2 PHE A 211 18.338 0.179 −32.489 1.00 9.24 A ATOM 1087 CZ PHE A 211 19.527 0.355 −31.797 1.00 8.29 A ATOM 1088 C PHE A 211 19.275 −0.107 −36.421 1.00 13.34 A ATOM 1089 O PHE A 211 20.108 −0.863 −35.901 1.00 12.59 A ATOM 1090 N GLN A 212 18.039 −0.495 −36.721 1.00 11.92 A ATOM 1091 CA GLN A 212 17.590 −1.860 −36.468 1.00 13.18 A ATOM 1092 CB GLN A 212 16.084 −1.968 −36.702 1.00 12.41 A ATOM 1093 CG GLN A 212 15.287 −1.129 −35.730 1.00 14.52 A ATOM 1094 CD GLN A 212 13.820 −1.126 −36.049 1.00 16.44 A ATOM 1095 OE1 GLN A 212 13.102 −2.070 −35.732 1.00 18.15 A ATOM 1096 NE2 GLN A 212 13.362 −0.067 −36.698 1.00 17.06 A ATOM 1097 C GLN A 212 18.341 −2.887 −37.313 1.00 13.31 A ATOM 1098 O GLN A 212 18.689 −3.976 −36.823 1.00 12.33 A ATOM 1099 N HIS A 213 18.584 −2.543 −38.574 1.00 12.02 A ATOM 1100 CA HIS A 213 19.326 −3.421 −39.470 1.00 13.70 A ATOM 1101 CB HIS A 213 19.485 −2.754 −40.845 1.00 15.78 A ATOM 1102 CG HIS A 213 20.385 −3.497 −41.785 1.00 16.70 A ATOM 1103 CD2 HIS A 213 21.733 −3.494 −41.917 1.00 18.08 A ATOM 1104 ND1 HIS A 213 19.914 −4.410 −42.704 1.00 19.47 A ATOM 1105 CE1 HIS A 213 20.932 −4.939 −43.361 1.00 18.40 A ATOM 1106 NE2 HIS A 213 22.047 −4.401 −42.901 1.00 18.23 A ATOM 1107 C HIS A 213 20.712 −3.679 −38.856 1.00 13.57 A ATOM 1108 O HIS A 213 21.184 −4.822 −38.832 1.00 13.81 A ATOM 1109 N GLU A 214 21.347 −2.621 −38.346 1.00 11.88 A ATOM 1110 CA GLU A 214 22.686 −2.741 −37.750 1.00 13.61 A ATOM 1111 CB GLU A 214 23.372 −1.374 −37.656 1.00 13.71 A ATOM 1112 CG GLU A 214 23.547 −0.614 −38.972 1.00 14.63 A ATOM 1113 CD GLU A 214 24.277 −1.403 −40.055 1.00 17.21 A ATOM 1114 OE1 GLU A 214 25.122 −2.266 −39.730 1.00 15.04 A ATOM 1115 OE2 GLU A 214 24.015 −1.132 −41.250 1.00 21.39 A ATOM 1116 C GLU A 214 22.671 −3.376 −36.361 1.00 14.65 A ATOM 1117 O GLU A 214 23.628 −4.041 −35.957 1.00 14.69 A ATOM 1118 N TYR A 215 21.594 −3.155 −35.620 1.00 16.18 A ATOM 1119 CA TYR A 215 21.488 −3.742 −34.298 1.00 15.85 A ATOM 1120 CB TYR A 215 20.218 −3.261 −33.587 1.00 17.67 A ATOM 1121 CG TYR A 215 20.067 −3.844 −32.196 1.00 21.32 A ATOM 1122 CD1 TYR A 215 20.887 −3.421 −31.148 1.00 19.48 A ATOM 1123 CE1 TYR A 215 20.798 −4.003 −29.883 1.00 20.09 A ATOM 1124 CD2 TYR A 215 19.143 −4.866 −31.940 1.00 20.98 A ATOM 1125 CE2 TYR A 215 19.046 −5.452 −30.680 1.00 20.75 A ATOM 1126 CZ TYR A 215 19.879 −5.020 −29.654 1.00 21.44 A ATOM 1127 OH TYR A 215 19.821 −5.626 −28.413 1.00 18.89 A ATOM 1128 C TYR A 215 21.452 −5.260 −34.472 1.00 14.58 A ATOM 1129 O TYR A 215 22.055 −6.007 −33.689 1.00 14.06 A ATOM 1130 N ASP A 216 20.750 −5.710 −35.506 1.00 13.46 A ATOM 1131 CA ASP A 216 20.657 −7.135 −35.787 1.00 14.06 A ATOM 1132 CB ASP A 216 19.780 −7.388 −37.008 1.00 13.61 A ATOM 1133 CG ASP A 216 18.308 −7.427 −36.671 1.00 13.64 A ATOM 1134 OD1 ASP A 216 17.957 −7.402 −35.475 1.00 12.49 A ATOM 1135 OD2 ASP A 216 17.495 −7.489 −37.611 1.00 15.97 A ATOM 1136 C ASP A 216 22.041 −7.720 −36.031 1.00 15.02 A ATOM 1137 O ASP A 216 22.353 −8.823 −35.557 1.00 16.95 A ATOM 1138 N HIS A 217 22.863 −6.988 −36.779 1.00 13.44 A ATOM 1139 CA HIS A 217 24.218 −7.433 −37.065 1.00 13.38 A ATOM 1140 CB HIS A 217 25.011 −6.350 −37.810 1.00 13.13 A ATOM 1141 CG HIS A 217 24.825 −6.370 −39.293 1.00 14.65 A ATOM 1142 CD2 HIS A 217 24.458 −5.397 −40.160 1.00 16.14 A ATOM 1143 ND1 HIS A 217 25.054 −7.495 −40.056 1.00 14.89 A ATOM 1144 CE1 HIS A 217 24.836 −7.214 −41.328 1.00 14.42 A ATOM 1145 NE2 HIS A 217 24.473 −5.948 −41.418 1.00 17.14 A ATOM 1146 C HIS A 217 24.906 −7.717 −35.736 1.00 14.40 A ATOM 1147 O HIS A 217 25.659 −8.684 −35.604 1.00 12.69 A ATOM 1148 N LEU A 218 24.644 −6.864 −34.750 1.00 14.83 A ATOM 1149 CA LEU A 218 25.255 −7.037 −33.445 1.00 14.51 A ATOM 1150 CB LEU A 218 25.053 −5.766 −32.611 1.00 12.54 A ATOM 1151 CG LEU A 218 25.713 −4.539 −33.285 1.00 17.61 A ATOM 1152 CD1 LEU A 218 25.643 −3.309 −32.390 1.00 16.94 A ATOM 1153 CD2 LEU A 218 27.180 −4.856 −33.619 1.00 14.59 A ATOM 1154 C LEU A 218 24.727 −8.291 −32.741 1.00 15.91 A ATOM 1155 O LEU A 218 25.375 −8.827 −31.846 1.00 17.34 A ATOM 1156 N GLU A 219 23.564 −8.774 −33.164 1.00 15.63 A ATOM 1157 CA GLU A 219 22.994 −9.983 −32.586 1.00 18.38 A ATOM 1158 CB GLU A 219 21.467 −9.865 −32.462 1.00 22.20 A ATOM 1159 CG GLU A 219 20.962 −8.892 −31.401 1.00 27.10 A ATOM 1160 CD GLU A 219 21.262 −9.346 −29.987 1.00 30.86 A ATOM 1161 OE1 GLU A 219 21.025 −10.535 −29.673 1.00 33.62 A ATOM 1162 OE2 GLU A 219 21.723 −8.510 −29.183 1.00 34.35 A ATOM 1163 C GLU A 219 23.327 −11.184 −33.477 1.00 17.11 A ATOM 1164 O GLU A 219 22.786 −12.272 −33.283 1.00 17.19 A ATOM 1165 N GLY A 220 24.220 −10.983 −34.444 1.00 14.72 A ATOM 1166 CA GLY A 220 24.580 −12.056 −35.356 1.00 12.31 A ATOM 1167 C GLY A 220 23.423 −12.355 −36.302 1.00 15.10 A ATOM 1168 O GLY A 220 23.401 −13.389 −36.979 1.00 14.67 A ATOM 1169 N VAL A 221 22.456 −11.437 −36.347 1.00 14.21 A ATOM 1170 CA VAL A 221 21.278 −11.581 −37.191 1.00 14.18 A ATOM 1171 CB VAL A 221 20.023 −11.047 −36.462 1.00 17.59 A ATOM 1172 CG1 VAL A 221 18.802 −11.120 −37.377 1.00 17.23 A ATOM 1173 CG2 VAL A 221 19.791 −11.844 −35.182 1.00 15.15 A ATOM 1174 C VAL A 221 21.418 −10.848 −38.529 1.00 14.45 A ATOM 1175 O VAL A 221 21.732 −9.657 −38.568 1.00 11.29 A ATOM 1176 N LEU A 222 21.176 −11.571 −39.620 1.00 13.92 A ATOM 1177 CA LEU A 222 21.269 −11.004 −40.965 1.00 15.74 A ATOM 1178 CB LEU A 222 21.972 −12.000 −41.893 1.00 13.26 A ATOM 1179 CG LEU A 222 23.492 −11.841 −42.001 1.00 13.73 A ATOM 1180 CD1 LEU A 222 24.070 −11.302 −40.699 1.00 13.62 A ATOM 1181 CD2 LEU A 222 24.119 −13.182 −42.379 1.00 12.93 A ATOM 1182 C LEU A 222 19.886 −10.639 −41.496 1.00 15.93 A ATOM 1183 O LEU A 222 18.906 −11.326 −41.198 1.00 16.25 A ATOM 1184 N PHE A 223 19.811 −9.579 −42.302 1.00 17.16 A ATOM 1185 CA PHE A 223 18.529 −9.097 −42.815 1.00 15.87 A ATOM 1186 CB PHE A 223 18.722 −7.817 −43.661 1.00 17.74 A ATOM 1187 CG PHE A 223 19.229 −8.044 −45.073 1.00 18.05 A ATOM 1188 CD1 PHE A 223 20.177 −9.023 −45.361 1.00 19.74 A ATOM 1189 CD2 PHE A 223 18.803 −7.207 −46.109 1.00 18.79 A ATOM 1190 CE1 PHE A 223 20.694 −9.161 −46.658 1.00 17.18 A ATOM 1191 CE2 PHE A 223 19.312 −7.333 −47.407 1.00 14.65 A ATOM 1192 CZ PHE A 223 20.259 −8.311 −47.680 1.00 18.55 A ATOM 1193 C PHE A 223 17.635 −10.089 −43.539 1.00 17.30 A ATOM 1194 O PHE A 223 16.408 −9.948 −43.493 1.00 16.29 A ATOM 1195 N PHE A 224 18.207 −11.103 −44.187 1.00 16.43 A ATOM 1196 CA PHE A 224 17.341 −12.058 −44.861 1.00 15.78 A ATOM 1197 CB PHE A 224 18.116 −12.898 −45.906 1.00 14.49 A ATOM 1198 CG PHE A 224 19.045 −13.945 −45.331 1.00 12.96 A ATOM 1199 CD1 PHE A 224 18.548 −15.152 −44.854 1.00 11.77 A ATOM 1200 CD2 PHE A 224 20.430 −13.742 −45.334 1.00 12.30 A ATOM 1201 CE1 PHE A 224 19.421 −16.150 −44.392 1.00 12.19 A ATOM 1202 CE2 PHE A 224 21.314 −14.720 −44.877 1.00 7.51 A ATOM 1203 CZ PHE A 224 20.812 −15.930 −44.405 1.00 13.32 A ATOM 1204 C PHE A 224 16.636 −12.923 −43.818 1.00 17.87 A ATOM 1205 O PHE A 224 15.608 −13.541 −44.115 1.00 16.51 A ATOM 1206 N ASP A 225 17.175 −12.930 −42.592 1.00 17.97 A ATOM 1207 CA ASP A 225 16.586 −13.692 −41.484 1.00 17.66 A ATOM 1208 CB ASP A 225 17.426 −13.586 −40.186 1.00 16.43 A ATOM 1209 CG ASP A 225 18.781 −14.305 −40.260 1.00 18.04 A ATOM 1210 OD1 ASP A 225 18.941 −15.266 −41.040 1.00 16.53 A ATOM 1211 OD2 ASP A 225 19.697 −13.911 −39.504 1.00 17.05 A ATOM 1212 C ASP A 225 15.182 −13.151 −41.163 1.00 18.56 A ATOM 1213 O ASP A 225 14.311 −13.894 −40.713 1.00 18.42 A ATOM 1214 N ARG A 226 14.969 −11.858 −41.386 1.00 18.50 A ATOM 1215 CA ARG A 226 13.681 −11.240 −41.072 1.00 21.41 A ATOM 1216 CB ARG A 226 13.915 −9.901 −40.360 1.00 22.31 A ATOM 1217 CG ARG A 226 14.890 −10.019 −39.186 1.00 25.19 A ATOM 1218 CD ARG A 226 15.206 −8.683 −38.564 1.00 28.37 A ATOM 1219 NE ARG A 226 14.317 −8.367 −37.451 1.00 32.73 A ATOM 1220 CZ ARG A 226 14.361 −8.965 −36.264 1.00 35.61 A ATOM 1221 NH1 ARG A 226 15.258 −9.916 −36.031 1.00 38.22 A ATOM 1222 NH2 ARG A 226 13.503 −8.621 −35.310 1.00 35.12 A ATOM 1223 C ARG A 226 12.758 −11.044 −42.279 1.00 21.52 A ATOM 1224 O ARG A 226 11.689 −10.447 −42.165 1.00 21.42 A ATOM 1225 N MET A 227 13.166 −11.559 −43.433 1.00 20.50 A ATOM 1226 CA MET A 227 12.345 −11.432 −44.628 1.00 20.39 A ATOM 1227 CB MET A 227 13.202 −11.585 −45.884 1.00 18.95 A ATOM 1228 CG MET A 227 14.359 −10.619 −45.971 1.00 18.23 A ATOM 1229 SD MET A 227 15.261 −10.828 −47.512 1.00 16.76 A ATOM 1230 CE MET A 227 16.117 −9.282 −47.571 1.00 16.68 A ATOM 1231 C MET A 227 11.275 −12.515 −44.620 1.00 19.32 A ATOM 1232 O MET A 227 11.432 −13.547 −43.969 1.00 17.02 A ATOM 1233 N THR A 228 10.180 −12.271 −45.324 1.00 19.28 A ATOM 1234 CA THR A 228 9.129 −13.269 −45.401 1.00 23.61 A ATOM 1235 CB THR A 228 7.854 −12.705 −46.062 1.00 23.79 A ATOM 1236 OG1 THR A 228 8.189 −12.120 −47.327 1.00 22.17 A ATOM 1237 CG2 THR A 228 7.213 −11.645 −45.165 1.00 20.55 A ATOM 1238 C THR A 228 9.671 −14.415 −46.247 1.00 26.65 A ATOM 1239 O THR A 228 10.715 −14.282 −46.899 1.00 25.82 A ATOM 1240 N ASP A 229 8.977 −15.544 −46.232 1.00 29.30 A ATOM 1241 CA ASP A 229 9.418 −16.689 −47.014 1.00 32.65 A ATOM 1242 CB ASP A 229 8.494 −17.890 −46.756 1.00 38.87 A ATOM 1243 CG ASP A 229 8.284 −18.172 −45.259 1.00 45.09 A ATOM 1244 OD1 ASP A 229 7.796 −17.274 −44.534 1.00 48.75 A ATOM 1245 OD2 ASP A 229 8.600 −19.298 −44.806 1.00 45.52 A ATOM 1246 C ASP A 229 9.401 −16.310 −48.503 1.00 32.03 A ATOM 1247 O ASP A 229 10.309 −16.660 −49.258 1.00 31.02 A ATOM 1248 N GLN A 230 8.374 −15.572 −48.913 1.00 31.00 A ATOM 1249 CA GLN A 230 8.238 −15.162 −50.305 1.00 31.22 A ATOM 1250 CB GLN A 230 6.884 −14.487 −50.533 1.00 32.85 A ATOM 1251 CG GLN A 230 5.709 −15.456 −50.531 1.00 37.00 A ATOM 1252 CD GLN A 230 4.364 −14.754 −50.639 1.00 38.18 A ATOM 1253 OE1 GLN A 230 4.100 −14.024 −51.601 1.00 38.74 A ATOM 1254 NE2 GLN A 230 3.502 −14.976 −49.650 1.00 37.86 A ATOM 1255 C GLN A 230 9.348 −14.243 −50.787 1.00 29.78 A ATOM 1256 O GLN A 230 9.902 −14.453 −51.869 1.00 29.39 A ATOM 1257 N VAL A 231 9.665 −13.217 −50.005 1.00 27.08 A ATOM 1258 CA VAL A 231 10.726 −12.303 −50.401 1.00 26.16 A ATOM 1259 CB VAL A 231 10.801 −11.080 −49.469 1.00 26.30 A ATOM 1260 CG1 VAL A 231 9.551 −10.231 −49.610 1.00 25.48 A ATOM 1261 CG2 VAL A 231 10.936 −11.536 −48.055 1.00 27.95 A ATOM 1262 C VAL A 231 12.050 −13.056 −50.371 1.00 25.45 A ATOM 1263 O VAL A 231 12.949 −12.789 −51.172 1.00 25.65 A ATOM 1264 N LEU A 232 12.162 −14.014 −49.456 1.00 24.04 A ATOM 1265 CA LEU A 232 13.379 −14.804 −49.345 1.00 22.95 A ATOM 1266 CB LEU A 232 13.304 −15.753 −48.148 1.00 23.20 A ATOM 1267 CG LEU A 232 14.562 −16.605 −47.940 1.00 24.20 A ATOM 1268 CD1 LEU A 232 15.782 −15.692 −47.782 1.00 25.17 A ATOM 1269 CD2 LEU A 232 14.390 −17.490 −46.718 1.00 25.41 A ATOM 1270 C LEU A 232 13.614 −15.606 −50.621 1.00 24.32 A ATOM 1271 O LEU A 232 14.745 −15.687 −51.113 1.00 23.37 A ATOM 1272 N ASP A 233 12.554 −16.206 −51.156 1.00 24.48 A ATOM 1273 CA ASP A 233 12.688 −16.974 −52.386 1.00 25.90 A ATOM 1274 CB ASP A 233 11.348 −17.582 −52.826 1.00 27.95 A ATOM 1275 CG ASP A 233 10.871 −18.694 −51.902 1.00 31.23 A ATOM 1276 OD1 ASP A 233 11.721 −19.352 −51.261 1.00 31.77 A ATOM 1277 OD2 ASP A 233 9.642 −18.922 −51.831 1.00 33.39 A ATOM 1278 C ASP A 233 13.209 −16.065 −53.490 1.00 24.49 A ATOM 1279 O ASP A 233 14.045 −16.477 −54.288 1.00 23.31 A ATOM 1280 N SER A 234 12.728 −14.822 −53.519 1.00 23.93 A ATOM 1281 CA SER A 234 13.144 −13.867 −54.546 1.00 24.19 A ATOM 1282 CB SER A 234 12.434 −12.522 −54.357 1.00 24.54 A ATOM 1283 OG SER A 234 13.044 −11.745 −53.341 1.00 26.38 A ATOM 1284 C SER A 234 14.655 −13.624 −54.609 1.00 24.31 A ATOM 1285 O SER A 234 15.154 −13.082 −55.591 1.00 26.53 A ATOM 1286 N ILE A 235 15.388 −14.006 −53.570 1.00 23.33 A ATOM 1287 CA ILE A 235 16.830 −13.808 −53.596 1.00 21.51 A ATOM 1288 CB ILE A 235 17.262 −12.641 −52.663 1.00 20.78 A ATOM 1289 CG2 ILE A 235 16.624 −11.329 −53.138 1.00 14.94 A ATOM 1290 CG1 ILE A 235 16.879 −12.964 −51.216 1.00 18.91 A ATOM 1291 CD1 ILE A 235 17.392 −11.968 −50.211 1.00 18.32 A ATOM 1292 C ILE A 235 17.616 −15.061 −53.215 1.00 22.26 A ATOM 1293 O ILE A 235 18.810 −14.983 −52.919 1.00 22.63 A ATOM 1294 N ARG A 236 16.958 −16.217 −53.229 1.00 22.15 A ATOM 1295 CA ARG A 236 17.637 −17.459 −52.882 1.00 23.00 A ATOM 1296 CB ARG A 236 16.685 −18.648 −53.003 1.00 24.18 A ATOM 1297 CG ARG A 236 15.802 −18.852 −51.786 1.00 28.66 A ATOM 1298 CD ARG A 236 14.937 −20.104 −51.903 1.00 30.02 A ATOM 1299 NE ARG A 236 14.181 −20.349 −50.678 1.00 31.89 A ATOM 1300 CZ ARG A 236 14.710 −20.823 −49.552 1.00 33.51 A ATOM 1301 NH1 ARG A 236 16.003 −21.115 −49.490 1.00 33.19 A ATOM 1302 NH2 ARG A 236 13.947 −20.989 −48.480 1.00 35.80 A ATOM 1303 C ARG A 236 18.865 −17.704 −53.758 1.00 24.86 A ATOM 1304 O ARG A 236 19.946 −18.026 −53.248 1.00 24.45 A ATOM 1305 N GLU A 237 18.698 −17.556 −55.073 1.00 23.40 A ATOM 1306 CA GLU A 237 19.802 −17.775 −55.996 1.00 22.38 A ATOM 1307 CB GLU A 237 19.339 −17.613 −57.450 1.00 21.86 A ATOM 1308 CG GLU A 237 18.187 −18.534 −57.832 1.00 26.01 A ATOM 1309 CD GLU A 237 18.347 −19.954 −57.284 1.00 28.79 A ATOM 1310 OE1 GLU A 237 19.326 −20.640 −57.649 1.00 31.36 A ATOM 1311 OE2 GLU A 237 17.487 −20.387 −56.479 1.00 31.54 A ATOM 1312 C GLU A 237 20.931 −16.803 −55.683 1.00 19.80 A ATOM 1313 O GLU A 237 22.102 −17.174 −55.709 1.00 18.95 A ATOM 1314 N GLU A 238 20.570 −15.567 −55.362 1.00 17.58 A ATOM 1315 CA GLU A 238 21.557 −14.546 −55.035 1.00 16.50 A ATOM 1316 CB GLU A 238 20.848 −13.219 −54.729 1.00 16.60 A ATOM 1317 CG GLU A 238 20.357 −12.449 −55.972 1.00 15.75 A ATOM 1318 CD GLU A 238 19.198 −13.120 −56.712 1.00 16.05 A ATOM 1319 OE1 GLU A 238 18.860 −12.653 −57.817 1.00 15.84 A ATOM 1320 OE2 GLU A 238 18.613 −14.097 −56.199 1.00 19.07 A ATOM 1321 C GLU A 238 22.449 −14.961 −53.851 1.00 16.83 A ATOM 1322 O GLU A 238 23.677 −14.877 −53.925 1.00 14.90 A ATOM 1323 N LEU A 239 21.820 −15.405 −52.764 1.00 15.47 A ATOM 1324 CA LEU A 239 22.542 −15.836 −51.574 1.00 16.39 A ATOM 1325 CB LEU A 239 21.553 −16.095 −50.428 1.00 14.91 A ATOM 1326 CG LEU A 239 20.700 −14.891 −50.006 1.00 17.17 A ATOM 1327 CD1 LEU A 239 19.828 −15.234 −48.796 1.00 15.12 A ATOM 1328 CD2 LEU A 239 21.617 −13.734 −49.679 1.00 15.57 A ATOM 1329 C LEU A 239 23.344 −17.100 −51.874 1.00 16.05 A ATOM 1330 O LEU A 239 24.430 −17.316 −51.331 1.00 14.99 A ATOM 1331 N GLU A 240 22.800 −17.927 −52.756 1.00 17.95 A ATOM 1332 CA GLU A 240 23.444 −19.169 −53.149 1.00 21.35 A ATOM 1333 CB GLU A 240 22.492 −19.969 −54.037 1.00 25.83 A ATOM 1334 CG GLU A 240 22.635 −21.471 −53.966 1.00 31.74 A ATOM 1335 CD GLU A 240 21.535 −22.176 −54.753 1.00 36.90 A ATOM 1336 OE1 GLU A 240 20.349 −21.810 −54.566 1.00 37.59 A ATOM 1337 OE2 GLU A 240 21.853 −23.092 −55.549 1.00 39.47 A ATOM 1338 C GLU A 240 24.740 −18.854 −53.903 1.00 19.90 A ATOM 1339 O GLU A 240 25.748 −19.548 −53.743 1.00 20.76 A ATOM 1340 N ALA A 241 24.711 −17.798 −54.710 1.00 18.49 A ATOM 1341 CA ALA A 241 25.887 −17.396 −55.480 1.00 18.34 A ATOM 1342 CB ALA A 241 25.515 −16.306 −56.483 1.00 19.10 A ATOM 1343 C ALA A 241 27.007 −16.905 −54.566 1.00 17.84 A ATOM 1344 O ALA A 241 28.183 −17.073 −54.881 1.00 17.32 A ATOM 1345 N LEU A 242 26.642 −16.289 −53.441 1.00 17.42 A ATOM 1346 CA LEU A 242 27.641 −15.794 −52.494 1.00 17.40 A ATOM 1347 CB LEU A 242 27.005 −14.800 −51.517 1.00 14.72 A ATOM 1348 CG LEU A 242 26.611 −13.447 −52.119 1.00 13.60 A ATOM 1349 CD1 LEU A 242 25.823 −12.653 −51.105 1.00 13.80 A ATOM 1350 CD2 LEU A 242 27.848 −12.675 −52.532 1.00 10.81 A ATOM 1351 C LEU A 242 28.267 −16.965 −51.730 1.00 18.23 A ATOM 1352 O LEU A 242 29.445 −16.925 −51.375 1.00 16.99 A ATOM 1353 N GLU A 243 27.472 −18.007 −51.494 1.00 19.15 A ATOM 1354 CA GLU A 243 27.941 −19.197 −50.792 1.00 20.79 A ATOM 1355 CB GLU A 243 26.770 −20.140 −50.507 1.00 21.06 A ATOM 1356 CG GLU A 243 25.848 −19.685 −49.378 1.00 19.76 A ATOM 1357 CD GLU A 243 24.475 −20.318 −49.474 1.00 20.44 A ATOM 1358 OE1 GLU A 243 24.357 −21.358 −50.150 1.00 22.37 A ATOM 1359 OE2 GLU A 243 23.518 −19.784 −48.873 1.00 20.73 A ATOM 1360 C GLU A 243 28.975 −19.912 −51.649 1.00 22.94 A ATOM 1361 O GLU A 243 29.983 −20.410 −51.143 1.00 22.58 A ATOM 1362 N LYS A 244 28.717 −19.963 −52.951 1.00 23.02 A ATOM 1363 CA LYS A 244 29.637 −20.601 −53.879 1.00 24.52 A ATOM 1364 CB LYS A 244 28.966 −20.798 −55.242 1.00 25.82 A ATOM 1365 CG LYS A 244 27.699 −21.650 −55.171 1.00 31.89 A ATOM 1366 CD LYS A 244 27.998 −23.064 −54.652 1.00 34.68 A ATOM 1367 CE LYS A 244 26.751 −23.745 −54.097 1.00 35.93 A ATOM 1368 NZ LYS A 244 26.233 −23.064 −52.871 1.00 36.31 A ATOM 1369 C LYS A 244 30.884 −19.735 −54.024 1.00 24.80 A ATOM 1370 O LYS A 244 32.005 −20.239 −53.979 1.00 24.15 A ATOM 1371 N LYS A 245 30.686 −18.431 −54.194 1.00 23.61 A ATOM 1372 CA LYS A 245 31.805 −17.503 −54.330 1.00 23.86 A ATOM 1373 CB LYS A 245 31.276 −16.075 −54.482 1.00 24.85 A ATOM 1374 CG LYS A 245 32.325 −14.977 −54.377 1.00 27.82 A ATOM 1375 CD LYS A 245 33.472 −15.174 −55.357 1.00 30.16 A ATOM 1376 CE LYS A 245 33.044 −14.966 −56.803 1.00 32.00 A ATOM 1377 NZ LYS A 245 34.179 −15.225 −57.737 1.00 29.90 A ATOM 1378 C LYS A 245 32.715 −17.609 −53.105 1.00 23.77 A ATOM 1379 O LYS A 245 33.938 −17.506 −53.207 1.00 21.14 A ATOM 1380 N TYR A 246 32.098 −17.827 −51.949 1.00 23.97 A ATOM 1381 CA TYR A 246 32.823 −17.966 −50.694 1.00 23.96 A ATOM 1382 CB TYR A 246 31.845 −18.110 −49.531 1.00 23.71 A ATOM 1383 CG TYR A 246 32.520 −18.412 −48.219 1.00 24.55 A ATOM 1384 CD1 TYR A 246 33.192 −17.415 −47.518 1.00 23.26 A ATOM 1385 CE1 TYR A 246 33.847 −17.697 −46.323 1.00 23.72 A ATOM 1386 CD2 TYR A 246 32.517 −19.705 −47.692 1.00 25.41 A ATOM 1387 CE2 TYR A 246 33.172 −19.998 −46.497 1.00 24.58 A ATOM 1388 CZ TYR A 246 33.835 −18.986 −45.821 1.00 24.76 A ATOM 1389 OH TYR A 246 34.501 −19.257 −44.647 1.00 25.79 A ATOM 1390 C TYR A 246 33.688 −19.210 −50.751 1.00 24.29 A ATOM 1391 O TYR A 246 34.864 −19.187 −50.386 1.00 23.22 A ATOM 1392 N GLU A 247 33.077 −20.302 −51.193 1.00 24.70 A ATOM 1393 CA GLU A 247 33.767 −21.569 −51.302 1.00 26.80 A ATOM 1394 CB GLU A 247 32.783 −22.658 −51.732 1.00 25.70 A ATOM 1395 CG GLU A 247 31.852 −23.115 −50.617 1.00 26.11 A ATOM 1396 CD GLU A 247 30.768 −24.069 −51.098 1.00 26.88 A ATOM 1397 OE1 GLU A 247 31.094 −25.045 −51.804 1.00 27.71 A ATOM 1398 OE2 GLU A 247 29.584 −23.848 −50.764 1.00 28.44 A ATOM 1399 C GLU A 247 34.916 −21.461 −52.297 1.00 27.97 A ATOM 1400 O GLU A 247 36.018 −21.937 −52.033 1.00 29.90 A ATOM 1401 N GLU A 248 34.660 −20.816 −53.428 1.00 29.20 A ATOM 1402 CA GLU A 248 35.675 −20.654 −54.460 1.00 31.97 A ATOM 1403 CB GLU A 248 35.073 −20.025 −55.726 1.00 34.39 A ATOM 1404 CG GLU A 248 35.868 −20.328 −57.004 1.00 40.86 A ATOM 1405 CD GLU A 248 35.930 −19.154 −57.983 1.00 44.67 A ATOM 1406 OE1 GLU A 248 34.864 −18.578 −58.313 1.00 47.37 A ATOM 1407 OE2 GLU A 248 37.052 −18.813 −58.432 1.00 44.21 A ATOM 1408 C GLU A 248 36.829 −19.780 −53.976 1.00 31.88 A ATOM 1409 O GLU A 248 37.993 −20.072 −54.255 1.00 31.42 A ATOM 1410 N LYS A 249 36.509 −18.708 −53.254 1.00 31.46 A ATOM 1411 CA LYS A 249 37.546 −17.803 −52.769 1.00 31.64 A ATOM 1412 CB LYS A 249 36.948 −16.456 −52.340 1.00 31.29 A ATOM 1413 CG LYS A 249 37.985 −15.524 −51.731 1.00 33.88 A ATOM 1414 CD LYS A 249 37.443 −14.145 −51.384 1.00 36.01 A ATOM 1415 CE LYS A 249 38.546 −13.266 −50.777 1.00 38.28 A ATOM 1416 NZ LYS A 249 38.102 −11.882 −50.419 1.00 39.36 A ATOM 1417 C LYS A 249 38.372 −18.371 −51.618 1.00 31.30 A ATOM 1418 O LYS A 249 39.598 −18.353 −51.672 1.00 31.00 A ATOM 1419 N THR A 250 37.708 −18.877 −50.584 1.00 30.44 A ATOM 1420 CA THR A 250 38.418 −19.414 −49.428 1.00 31.23 A ATOM 1421 CB THR A 250 37.555 −19.338 −48.148 1.00 31.86 A ATOM 1422 OG1 THR A 250 36.507 −20.314 −48.214 1.00 34.34 A ATOM 1423 CG2 THR A 250 36.941 −17.952 −48.001 1.00 34.00 A ATOM 1424 C THR A 250 38.892 −20.857 −49.586 1.00 30.95 A ATOM 1425 O THR A 250 39.942 −21.223 −49.065 1.00 29.91 A ATOM 1426 N GLY A 251 38.125 −21.668 −50.306 1.00 30.20 A ATOM 1427 CA GLY A 251 38.491 −23.064 −50.475 1.00 30.06 A ATOM 1428 C GLY A 251 37.843 −23.878 −49.365 1.00 30.74 A ATOM 1429 O GLY A 251 38.060 −25.083 −49.238 1.00 31.77 A ATOM 1430 N LEU A 252 37.030 −23.193 −48.564 1.00 29.90 A ATOM 1431 CA LEU A 252 36.323 −23.790 −47.440 1.00 27.62 A ATOM 1432 CB LEU A 252 36.561 −22.942 −46.191 1.00 27.01 A ATOM 1433 CG LEU A 252 38.024 −22.633 −45.872 1.00 25.71 A ATOM 1434 CD1 LEU A 252 38.102 −21.489 −44.875 1.00 25.85 A ATOM 1435 CD2 LEU A 252 38.701 −23.888 −45.330 1.00 24.69 A ATOM 1436 C LEU A 252 34.823 −23.840 −47.736 1.00 27.80 A ATOM 1437 O LEU A 252 34.306 −23.006 −48.480 1.00 27.40 A ATOM 1438 N PRO A 253 34.109 −24.822 −47.159 1.00 27.39 A ATOM 1439 CD PRO A 253 34.659 −25.921 −46.355 1.00 27.81 A ATOM 1440 CA PRO A 253 32.663 −24.994 −47.344 1.00 28.16 A ATOM 1441 CB PRO A 253 32.399 −26.394 −46.784 1.00 28.26 A ATOM 1442 CG PRO A 253 33.756 −27.045 −46.736 1.00 28.79 A ATOM 1443 C PRO A 253 31.954 −23.931 −46.506 1.00 29.29 A ATOM 1444 O PRO A 253 32.331 −23.707 −45.355 1.00 30.16 A ATOM 1445 N SER A 254 30.931 −23.283 −47.054 1.00 30.59 A ATOM 1446 CA SER A 254 30.231 −22.248 −46.286 1.00 32.13 A ATOM 1447 CB SER A 254 29.629 −21.192 −47.219 1.00 31.94 A ATOM 1448 OG SER A 254 28.478 −21.688 −47.880 1.00 30.37 A ATOM 1449 C SER A 254 29.114 −22.815 −45.423 1.00 32.34 A ATOM 1450 O SER A 254 28.543 −23.851 −45.742 1.00 30.85 A ATOM 1451 N PRO A 255 28.808 −22.150 −44.299 1.00 34.62 A ATOM 1452 CD PRO A 255 29.704 −21.193 −43.627 1.00 33.82 A ATOM 1453 CA PRO A 255 27.736 −22.594 −43.393 1.00 35.62 A ATOM 1454 CB PRO A 255 28.082 −21.906 −42.079 1.00 36.32 A ATOM 1455 CG PRO A 255 29.590 −21.635 −42.200 1.00 35.07 A ATOM 1456 C PRO A 255 26.410 −22.096 −43.984 1.00 38.43 A ATOM 1457 O PRO A 255 25.564 −21.528 −43.295 1.00 37.08 A ATOM 1458 N GLU A 256 26.273 −22.334 −45.287 1.00 42.39 A ATOM 1459 CA GLU A 256 25.139 −21.942 −46.124 1.00 45.09 A ATOM 1460 CB GLU A 256 25.419 −22.388 −47.564 1.00 48.71 A ATOM 1461 CG GLU A 256 24.872 −23.776 −47.940 1.00 51.06 A ATOM 1462 CD GLU A 256 25.525 −24.911 −47.177 1.00 54.43 A ATOM 1463 OE1 GLU A 256 26.723 −25.180 −47.422 1.00 54.78 A ATOM 1464 OE2 GLU A 256 24.840 −25.533 −46.334 1.00 54.37 A ATOM 1465 C GLU A 256 23.721 −22.388 −45.759 1.00 45.88 A ATOM 1466 O GLU A 256 23.420 −22.700 −44.607 1.00 46.95 A ATOM 1467 N ARG A 257 22.875 −22.396 −46.795 1.00 47.40 A ATOM 1468 CA ARG A 257 21.458 −22.766 −46.768 1.00 48.03 A ATOM 1469 CB ARG A 257 21.166 −23.841 −45.708 1.00 49.00 A ATOM 1470 CG ARG A 257 19.673 −24.239 −45.527 1.00 49.58 A ATOM 1471 CD ARG A 257 18.926 −24.462 −46.845 1.00 50.25 A ATOM 1472 NE ARG A 257 18.716 −23.197 −47.542 1.00 50.22 A ATOM 1473 CZ ARG A 257 19.098 −22.961 −48.791 1.00 51.01 A ATOM 1474 NH1 ARG A 257 19.705 −23.913 −49.485 1.00 51.87 A ATOM 1475 NH2 ARG A 257 18.900 −21.767 −49.332 1.00 51.93 A ATOM 1476 C ARG A 257 20.576 −21.545 −46.548 1.00 48.27 A ATOM 1477 O ARG A 257 19.959 −21.445 −45.465 1.00 48.75 A ATOM 1478 OXT ARG A 257 20.517 −20.700 −47.471 1.00 47.21 A ATOM 1479 S SO4 L 1 26.750 −1.543 −20.726 1.00 38.59 L ATOM 1480 O1 SO4 L 1 26.466 −2.892 −21.261 1.00 36.34 L ATOM 1481 O2 SO4 L 1 25.516 −0.950 −20.178 1.00 38.18 L ATOM 1482 O3 SO4 L 1 27.748 −1.640 −19.643 1.00 39.55 L ATOM 1483 O4 SO4 L 1 27.270 −0.687 −21.812 1.00 36.64 L ATOM 1484 ZN + 2 ZN2 M 1 24.054 −4.948 −43.032 1.00 17.46 M ATOM 1485 ZN + 2 ZN2 M 2 39.953 7.918 −41.358 1.00 25.22 M ATOM 1486 ZN + 2 ZN2 M 3 36.946 −5.734 −22.999 1.00 22.38 M ATOM 1487 ZN + 2 ZN2 M 4 19.157 −22.594 −56.610 0.50 43.08 M ATOM 1488 ZN + 2 ZN2 M 5 21.794 −10.556 −27.675 0.40 29.27 M ATOM 1489 ZN + 2 ZN2 M 6 −0.285 1.757 −30.184 0.50 36.10 M ATOM 1490 OH2 TIP S 1 25.969 −2.074 −44.807 1.00 14.25 S ATOM 1491 OH2 TIP S 2 3.811 2.346 −30.357 1.00 14.25 S ATOM 1492 OH2 TIP S 3 −0.051 0.258 −28.134 1.00 14.25 S ATOM 1493 OH2 TIP S 4 10.090 −8.668 −43.625 1.00 15.50 S ATOM 1494 OH2 TIP S 5 24.192 −17.873 −42.585 1.00 9.05 S ATOM 1495 OH2 TIP S 6 26.335 −9.687 −38.091 1.00 2.09 S ATOM 1496 OH2 TIP S 7 42.910 −1.393 −27.043 1.00 40.60 S ATOM 1497 OH2 TIP S 8 22.287 −8.014 −43.054 1.00 3.78 S ATOM 1498 OH2 TIP S 9 22.996 −4.825 −50.565 1.00 6.81 S ATOM 1499 OH2 TIP S 10 9.921 −9.608 −46.068 1.00 10.87 S ATOM 1500 OH2 TIP S 11 21.456 −25.782 −55.836 1.00 28.41 S ATOM 1501 OH2 TIP S 12 31.066 7.682 −53.311 1.00 21.03 S ATOM 1502 OH2 TIP S 13 11.349 −7.646 −52.115 1.00 13.10 S ATOM 1503 OH2 TIP S 14 24.496 −4.224 −28.092 1.00 23.20 S ATOM 1504 OH2 TIP S 15 20.931 −22.429 −58.425 1.00 14.25 S ATOM 1505 OH2 TIP S 16 27.530 −14.722 −42.923 1.00 9.87 S ATOM 1506 OH2 TIP S 17 9.342 6.275 −38.471 1.00 18.89 S ATOM 1507 OH2 TIP S 18 5.984 −3.364 −30.710 1.00 11.90 S ATOM 1508 OH2 TIP S 19 19.793 −0.210 −46.871 1.00 26.54 S ATOM 1509 OH2 TIP S 20 28.046 −17.680 −41.836 1.00 10.88 S ATOM 1510 OH2 TIP S 23 21.557 −7.309 −40.376 1.00 14.41 S ATOM 1511 OH2 TIP S 24 12.004 1.128 −39.615 1.00 16.43 S ATOM 1512 OH2 TIP S 25 30.777 −14.876 −50.134 1.00 11.00 S ATOM 1513 OH2 TIP S 26 −1.303 −0.882 −25.776 1.00 38.49 S ATOM 1514 OH2 TIP S 28 13.901 −4.350 −36.733 1.00 17.30 S ATOM 1515 OH2 TIP S 30 28.137 −11.377 −35.724 1.00 13.45 S ATOM 1516 OH2 TIP S 32 10.937 −8.045 −38.922 1.00 19.04 S ATOM 1517 OH2 TIP S 33 32.844 −9.803 −54.314 1.00 43.74 S ATOM 1518 OH2 TIP S 34 36.191 −3.234 −48.811 1.00 43.05 S ATOM 1519 OH2 TIP S 36 16.139 −16.545 −56.285 1.00 35.15 S ATOM 1520 OH2 TIP S 37 33.130 11.162 −16.863 1.00 27.08 S ATOM 1521 OH2 TIP S 38 13.131 −19.278 −54.777 1.00 21.83 S ATOM 1522 OH2 TIP S 39 26.597 −10.167 −54.360 1.00 17.41 S ATOM 1523 OH2 TIP S 40 12.308 −8.028 −32.094 1.00 23.20 S ATOM 1524 OH2 TIP S 41 23.225 −15.656 −35.045 1.00 28.13 S ATOM 1525 OH2 TIP S 42 24.923 −2.981 −42.626 1.00 13.51 S ATOM 1526 OH2 TIP S 43 44.298 −1.798 −33.197 1.00 17.76 S ATOM 1527 OH2 TIP S 44 20.680 −0.619 −44.292 1.00 14.01 S ATOM 1528 OH2 TIP S 45 5.896 −15.409 −44.351 1.00 22.87 S ATOM 1529 OH2 TIP S 46 23.233 −24.442 −53.915 1.00 39.19 S ATOM 1530 OH2 TIP S 47 14.208 −10.403 −32.245 1.00 18.95 S ATOM 1531 OH2 TIP S 48 38.832 −0.501 −27.020 1.00 14.49 S ATOM 1532 OH2 TIP S 49 18.236 −0.002 −44.579 1.00 27.51 S ATOM 1533 OH2 TIP S 50 36.434 8.748 −34.776 1.00 11.42 S ATOM 1534 OH2 TIP S 51 27.579 14.569 −38.647 1.00 28.40 S ATOM 1535 OH2 TIP S 52 38.153 2.185 −20.385 1.00 15.38 S ATOM 1536 OH2 TIP S 54 29.121 −17.432 −57.522 1.00 14.06 S ATOM 1537 OH2 TIP S 55 28.554 −19.346 −40.014 1.00 37.78 S ATOM 1538 OH2 TIP S 56 22.082 −22.880 −50.314 1.00 24.72 S ATOM 1539 OH2 TIP S 59 35.171 −10.112 −50.196 1.00 27.04 S ATOM 1540 OH2 TIP S 61 9.233 −20.875 −49.991 1.00 31.75 S ATOM 1541 OH2 TIP S 62 18.870 −7.844 −55.461 1.00 34.62 S ATOM 1542 OH2 TIP S 63 11.323 3.689 −39.850 1.00 18.17 S ATOM 1543 OH2 TIP S 64 35.403 9.921 −37.907 1.00 26.55 S ATOM 1544 OH2 TIP S 65 8.090 14.529 −43.710 1.00 30.17 S ATOM 1545 OH2 TIP S 66 38.045 −0.048 −19.192 1.00 30.52 S ATOM 1546 OH2 TIP S 67 33.352 −13.694 −29.289 1.00 33.68 S ATOM 1547 OH2 TIP S 69 35.976 −15.780 −40.760 1.00 13.56 S

The examples set forth above are provided to give those of ordinary skill in the art a complete disclosure and description of how to make and use the embodiments of the devices, systems and methods of the invention, and are not intended to limit the scope of what the inventors regard as their invention. Modifications of the above-described modes for carrying out the invention that are obvious to persons of skill in the art are intended to be within the scope of the following claims. All patents and publications mentioned in the specification are indicative of the levels of skill of those skilled in the art to which the invention pertains. All references cited in this disclosure are incorporated by reference to the same extent as if each reference had been incorporated by reference in its entirety individually.

In addition, it is understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although any methods and materials similar or equivalent to those described herein can be used in the practice for testing of the invention(s), specific examples of appropriate materials and methods are described herein.

A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims. 

What is claimed is:
 1. A method of identifying a candidate compound that binds to the active site of Arabidopsis thaliana peptide deformylase polypeptide, the method comprising: a) comparing, by a processor of a computer, the atomic structure of the compound with a three-dimensional structure of a crystalline form of an Arabidopsis thaliana peptide deformylase polypeptide, wherein the crystalline form of the polypeptide consists of the amino acid sequence of SEQ ID NO:1 complexed with Zn²⁺, wherein said crystalline form has the space group symmetry P4₁2₁2; unit cell dimensions of a=about 49 angstroms to about 52 angstroms, b=about 49 angstroms to about 52 angstroms, and c=about 143 angstroms to about 147 angstroms; and alpha=beta=gamma=90 degrees; and b) computationally identifying by the processor a candidate compound for an ability to bind to the Arabidopsis thaliana peptide deformylase wherein said computer has the atomic coordinates of said polypeptide stored therein, and wherein said three-dimensional structure is generated from the structure coordinates of Table 1 or homologous structures coordinates for the amino acid residues of SEQ ID NO: 1 comprising a root mean square deviation of non-hydrogen atoms of less than about 0.35 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table
 1. 2. The method of claim 1, wherein the candidate compound binds to the active site of the Arabidopsis thaliana peptide deformylase.
 3. The method of claim 1, wherein the three-dimensional structure is generated from the structure coordinates for one or more Arabidopsis thaliana peptide deformylase amino acid residues Gly121, Gly123, Leu124, Gln128, Glu169, Gly170, Cys171, Leu172, His213, Glu214, His217, and Tyr178 according to Table 1, or similar structure coordinates for said amino acids comprising a root mean square deviation of non-hydrogen atoms of less than about 0.35 Å when superimposed on the non-hydrogen atom positions of the corresponding atomic coordinates of Table
 1. 4. The method of claim 1, wherein the comparing comprises employing a computational means to perform a fitting operation between the compound and at least one binding site of the peptide deformylase.
 5. The method of claim 1, further comprising synthesizing the candidate compound and screening the candidate compound for the ability to bind Arabidopsis thaliana peptide deformylase in vitro or in vivo.
 6. The method of claim 5, wherein the compound is an herbicide.
 7. A method of computationally designing a candidate compound that binds to Arabidopsis thaliana peptide deformylase polypeptide, the method comprising: a) comparing by a processor of a computer the atomic structure of chemical entities, or fragments thereof, with a three-dimensional structural representation of a crystalline form of a polypeptide; b) computationally identifying by the processor chemical entities capable of associating with the three-dimensional structural representation of a crystalline form of a polypeptide; and c) assembling the chemical entities, or fragments thereof, into a single molecule to provide the structure of the candidate compound wherein the crystalline form of the polypeptide consists of the amino acid sequence of SEQ ID NO:1 complexed with Zn²⁺, wherein said crystalline form has the space group symmetry P4₁2₁2; unit cell dimensions of a=about 49 angstroms to about 52 angstroms, b=about 49 angstroms to about 52 angstroms, and c=about 143 angstroms to about 147 angstroms; and alpha=beta=gamma=90 degrees wherein said computer has the atomic coordinates of said polypeptide stored therein.
 8. The method of claim 7, wherein the candidate compound binds to the active site of Arabidopsis thaliana peptide deformylase.
 9. The method of claim 7 further comprising synthesizing the candidate compound and screening the candidate compound for Arabidopsis thaliana peptide deformylase binding activity. 